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NUT carcinoma (NC) is a rare, aggressive, and genetically defined epithelial malignancy characterized by rearrangements involving the NUTM1 gene, most commonly BRD4::NUTM1 fusions. Although classically and initially described as involving midline location, especially the sinonasal region of children and young adults, NC has been found to have myriad localizations and age affliction, with primary pulmonary involvement being exceedingly uncommon. A 60-year-old female presented with a non-productive cough, weight loss, and anorexia. Imaging revealed a right upper lobe lung mass with mediastinal involvement and subcarinal lymphadenopathy. Biopsy demonstrated an undifferentiated carcinoma with focal abrupt keratinization and immunohistochemically the tumor exhibited strong positivity for p40 and NUT protein, confirming the diagnosis of NC. PD-L1 testing revealed a tumor proportion score (TPS) of 70%. Next-generation sequencing identified a rare WHSC1L1::NUTM1 fusion. The patient was treated with paclitaxel and carboplatin with partial thoracic response; however, new skeletal metastases developed, and she was transitioned to palliative care.

HER2-positive metastatic breast cancer (MBC) represents a challenging subtype of breast cancer, characterized by aggressive disease and poor clinical outcomes. Trastuzumab emtansine (TDM1), an antibody–drug conjugate combining trastuzumab and emtansine, has demonstrated efficacy in clinical trials as a second-line treatment for patients progressing after prior therapies. This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients. A retrospective analysis was conducted on 70 HER2-positive MBC patients treated with TDM1 at our centre between January 2020 and December 2022. Clinical characteristics, progression-free survival (PFS), overall survival (OS), response rates, and toxicity were evaluated using hospital records. PFS and OS were calculated using Kaplan–Meier methods, and survival curves were compared with log-rank tests. The median age of patients was 47 years, with a majority presenting with advanced disease and prior treatment lines. The median PFS was 6.1 months (95% CI, 4.5–7.6), and the median OS was 14.4 months (95% CI, 10.2–18.0). The objective response rate was 75.7%, with 12.8% achieving a complete response and 62.8% a partial response. PFS was significantly longer in hormone receptor-positive patients compared to hormone receptor-negative patients (8.1 vs. 4.1 months, p = 0.035). Toxicity was manageable, with grade 3–4 adverse events including elevated transaminases (8.5%), thrombocytopenia (5.7%), and anemia (4.2%). The efficacy of TDM1 in this real-world cohort aligns with clinical trial data, though PFS and OS were somewhat lower compared to trials, likely due to the inclusion of patients with more extensive disease and prior treatments. Notably, TDM1 demonstrated activity against CNS metastases and a manageable safety profile, with higher incidence of hepatic and hematologic toxicities. Our study supports the use of TDM1 as a viable option for treating HER2-positive MBC in routine clinical practice, confirming its effectiveness and safety profile observed in clinical trials.

Introduction and Objective: Food insecurity (FI) is associated with adverse health outcomes across the lifespan. Primary care and prenatal practices can identify and address FI among patients through screening and interventions. It is unclear how practices and communities responded to FI during the COVID-19 pandemic, and how the pandemic may have impacted practices’ FI strategies. We aimed to understand how practices providing primary care or prenatal care in northern New England experienced changes in FI during the COVID-19 pandemic. Methods: We conducted a web-based survey of clinicians and staff from 43 unique practices providing primary care or prenatal care in northern New England. Results: Most practices (59.5%) reported at least 1 new food program in the practice or community since the pandemic began. Practices reporting new practice- or community-based food programs were more likely to be rural, federally qualified health centers, and have greater confidence in practice and community capacity to address FI (chi-square tests, P < .05). Conclusion: Results suggest that practices and surrounding communities in northern New England responded to FI during the pandemic by increasing food support programs. Future work is needed to examine the impact of food programs initiated during the pandemic and determine optimal strategies for practices to address FI among patients.

Background Food insecurity (FI) is associated with negative health outcomes and increased healthcare utilization. Rural populations face increased rates of FI and encounter additional barriers to achieving food security. We sought to identify barriers and facilitators to screening and interventions for FI in rural primary care practices. Methods We conducted a mixed-methods study using surveys and semi-structured interviews of providers and staff members from rural primary care practices in northern New England. Survey data were analyzed descriptively, and thematic analysis was used to identify salient interview themes. Results Participants from 24 rural practices completed the survey, and 13 subsequently completed an interview. Most survey respondents (54%) reported their practices systematically screen for FI and 71% reported food needs were “very important” for their patients and communities. Time and resource constraints were the most frequently cited barriers to screening for and addressing FI in practices based on survey results. Interview themes were categorized by screening and intervention procedures, community factors, patient factors, external factors, practice factors, process and implementation factors, and impact of FI screening and interventions. Time and resource constraints were a major theme in interviews, and factors attributed to rural practice settings included geographically large service areas, stigma from loss of privacy in small communities, and availability of food resources through farming. Conclusions Rural primary care practices placed a high value on addressing food needs but faced a variety of barriers to implementing and sustaining FI screening and interventions. Strategies that utilize practice strengths and address time and resource constraints, stigma, and large service areas could promote the adoption of novel interventions to address FI.

Medical students engage with medically underserved communities (MUC) and vulnerable populations but often lack preparation to advocate appropriately for these communities. While preclinical programs with an experiential community component effectively increase knowledge about serving MUC, the pandemic limited clinical opportunities in community settings for learners. We examined the impact of a streamlined, hybrid service learning curriculum on first-year medical student attitudes towards MUC and their readiness and interest in addressing health barriers faced by this population. The redesigned curriculum for the student-led program required participants to attend nine virtual seminars led by faculty and community members with expertise serving MUC. Students partnered with one of three community agencies to organize service projects and gain exposure to the life experiences of MUC using virtual and in-person approaches. Of the fifteen first year medical students who participated in the program, positive attitudes were sustained across all scales using the Medical Student Attitudes Toward the Underserved (MSATU) questionnaire after one year. A majority (≥50%) of students reported a large increase in their knowledge of the health challenges faced by underserved populations after each didactic session. Despite the mostly virtual nature of community partnerships, students reported increased confidence in their ability to direct MUC patients to local resources (p < 0.01). The program also had a positive impact on student interest in working with medically underserved patients in the future, with 71% of participants indicating a significant impact on their interest in working in a medically underserved area. Our redesigned elective curriculum provided participants with foundational knowledge to advocate appropriately for underserved populations and demonstrated the efficacy of virtual approaches for community service and service learning. Our findings suggest hybrid and virtual experiential learning opportunities are a viable and non-inferior curricular approach to teaching health equity and community health.

Background Food insecurity during pregnancy has important implications for maternal and newborn health. There is increasing commitment to screening for social needs within health care settings. However, little is known about current screening processes or the capacity for prenatal care clinics to address food insecurity among their patients. We aimed to assess barriers and facilitators prenatal care clinics face in addressing food insecurity among pregnant people and to identify opportunities to improve food security among this population. Methods We conducted a qualitative study among prenatal care clinics in New Hampshire and Vermont. Staff and clinicians engaged in food security screening and intervention processes at clinics affiliated with the Northern New England Perinatal Quality Improvement Network (NNEPQIN) were recruited to participate in key informant interviews. Thematic analysis was used to identify prominent themes in the interview data. Results Nine staff members or clinicians were enrolled and participated in key informant interviews. Key barriers to food security screening and interventions included lack of protocols and dedicated staff at the clinic as well as community factors such as availability of food distribution services and transportation. Facilitators of screening and intervention included a supportive culture at the clinic, trusting relationships between patients and clinicians, and availability of clinic-based and community resources. Conclusion Prenatal care settings present an important opportunity to identify and address food insecurity among pregnant people, yet most practices lack specific protocols for screening. Our findings indicate that more systematic processes for screening and referrals, dedicated staff, and onsite food programs that address transportation and other access barriers could improve the capacity of prenatal care clinics to improve food security during pregnancy.

We have previously proposed that uterine caspase-3 may modulate uterine contractility in a gestationally regulated fashion. The objective of this study was to determine the mechanism by which uterine caspase-3 is activated and consequently controlled in the pregnant uterus across gestation. Utilizing the mouse uterus as our gestational model we examined the intrinsic and extrinsic apoptotic signaling pathways and the endoplasmic reticulum stress response as potential activators of uterine caspase-3 at the transcriptional and translational level. Our study revealed robust activation of the uterine myocyte endoplasmic reticulum stress response and its adaptive unfolded protein response during pregnancy coinciding respectively with increased uterine caspase-3 activity and its withdrawal to term. In contrast the intrinsic and extrinsic apoptotic signaling pathways remained inactive across gestation. We speculate that physiological stimuli experienced by the pregnant uterus likely potentiates the uterine myocyte endoplasmic reticulum stress response resulting in elevated caspase-3 activation, which is isolated to the pregnant mouse myometrium. However as term approaches, activation of an elevated adaptive unfolded protein response acts to limit the endoplasmic reticulum stress response inhibiting caspase-3 resulting in its decline towards term. We speculate that these events have the capacity to regulate gestational length in a caspase-3 dependent manner.

Nearly all cervical cancers are caused by persistent high-risk human papillomavirus (hrHPV) infection. There are 14 recognized hrHPV genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), and hrHPV genotypes 16 and 18 comprise approximately 66% of all cases worldwide. An additional 15% of cervical cancers are caused by hrHPV genotypes 31, 33, 45, 52, and 58. Screening patients for hrHPV as a mechanism for implementation of early treatment is a proven strategy for decreasing the incidence of HPV-related neoplasia, cervical cancer in particular. Here, we present population data from an HPV screening initiative in Kosovo designed to better understand the prevalence of the country’s HPV burden and local incidence of cervical cancer by hrHPV genotype. Nearly 2000 women were screened for hrHPV using a real-time polymerase chain reaction (real-time PCR) assay followed by melt curve analysis to establish the prevalence of hrHPV in Kosovo. Additionally, DNA was extracted from 200 formalin-fixed, paraffin embedded cervical tumors and tested for hrHPV using the same method. Cervical screening samples revealed a high prevalence of hrHPV genotypes 16 and 51, while cervical cancer specimens predominantly harbored genotypes 16, 18, and 45. This is the first comprehensive screening study for evaluating the prevalence of hrHPV genotypes in Kosovo on screening cervical brush samples and cervical neoplasms. Given the geographic distribution of hrHPV genotypes and the WHO’s global initiative to eliminate cervical cancer, this study can support and direct vaccination efforts to cover highly prevalent hrHPV genotypes in Kosovo’s at-risk population.

Aplastic anaemia is often associated with recent viral illnesses to include EBV and parvovirus along with certain medications such as anticonvulsants and sulfa containing antibiotics. We describe a case report of a female patient in her 70s who presented with pancytopenia after being treated with nitrofurantoin and ciprofloxacin for suspected urinary tract infection. She underwent an extensive workup to rule out alternative aetiologies of her pancytopenia to include a broad viral, autoimmune and malignancy evaluation which were unrevealing. Given her recent exposure to ciprofloxacin and nitrofurantoin and marrow recovery following removal of these agents, it was presumed that antibiotic exposure was the underlying cause of her aplastic anaemia.

This thesis comprises two distinct, albeit closely related, parts. In the first part, we improve on a construction of Mestre--Shioda to produce infinite families of hyperelliptic curves having a record number of rational points and Mordell--Weil rank. In the second part, we give a unified treatment of work of Mestre--Shioda and Liu--Lorenzini, and by generalizing a Specialization Theorem of Néron, we construct families of abelian varieties which realize specified Galois representations.