Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and characterization of O-linked glycans in cervical mucus as biomarkers of sperm transport: A novel sheep model

Abstract Cervical mucus plays an important role in female fertility, since it allows the entry of motile and morphological normal sperm while preventing the ascent of pathogens from the vagina. The function of cervical mucus is critically linked to its rheological properties that are in turn dictated by O-glycosylated proteins, called mucins. We aimed to characterize the O-glycan composition in the cervical mucus of six European ewe breeds with known differences in pregnancy rates following cervical/vaginal artificial insemination with frozen–thawed semen, which are due to reported differences in cervical sperm transport. These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway (n = 28–30 ewes/breed). We identified 124 O-glycans, from which 51 were the major glycans with core 2 and fucosylated glycans as the most common structures. The use of exogenous hormones for synchronization did not affect the O-glycan composition in both high-fertility ewe breeds, but it did in the other four ewe breeds. There was a higher abundance of the sulfated glycan (Galβ1–3[SO3-GlcNAcβ1–6]GalNAc), fucosylated glycan (GlcNAcβ1–3(Fucα1–2Galβ1–3)GalNAc) and core 4 glycan (GlcNAcβ1–3[GlcNAcβ1–6]GalNAc) in the low-fertility Suffolk breed compared with NWS (high fertility). In addition, core 4 glycans were negatively correlated with mucus viscosity. This novel study has identified O-glycans that are important for cervical sperm transport and could have applications across a range of species including human.
MicroRNA‐132 is involved in morphine dependence via modifying the structural plasticity of the dentate gyrus neurons in rats

Repeated morphine exposure has been shown to induce neuronal plasticity in reward‐related areas of the brain. miR‐132, a CREB‐induced and activation‐dependent microRNA, has been suggested to be involved in the neuronal plasticity by increasing neuronal dendritic branches and spinogenesis. However, it is still unclear whether miR‐132 is related to morphine dependence. Here, we investigate whether miR‐132 is involved in morphine dependence and whether it is related to the structural plasticity of the dentate gyrus (DG) neurons. Sprague–Dawley rats are treated with increasing doses of morphine injection for six consecutive days to develop morphine dependence. Our results show that dendritic branching and spinogenesis of the DG neurons of morphine dependent rats are increased. Morphine treatment (24 h) promotes the differentiation of N2a cells stably expressing μ‐opioid receptor by up‐regulating miR‐132 expression. Moreover, inhibiting miR‐132 3p (but not 5p) of the DG neurons can reverse the structural plasticity and disrupt the formation of morphine dependence in rats. These findings indicate that miR‐132 in the DG neurons is involved in morphine dependence via modifying the neuronal plasticity.
Exercise Experiences of Older Adults with Diabetes and Sarcopenia: A Phenomenological Study

Sarcopenia is a common and progressive skeletal muscle condition, often described as an intermediate stage in the development of frailty and disability in patients with diabetes. This can be improved through physical activity and exercise. This descriptive phenomenological study explored the exercise experiences of older adults with diabetes and sarcopenia. Individual interviews were conducted following semi-structured interview guidelines, and narratives were analyzed using Giorgi’s method. Data saturation was achieved after interviewing 14 purposively sampled older patients with diabetes and sarcopenia. The study identified three main themes: encountering difficulty during exercise, recognizing the advantages of exercise, and constructing a suitable exercise model. While older adults with diabetes and sarcopenia may encounter difficulty during exercise, they also experience positive feedback from exercise. Understanding the limitations of older adults, individualizing exercise models based on their exercise experiences, and providing appropriate interventions and necessary emotional support can effectively prevent diabetes and sarcopenia.
Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

Purpose Angiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing rare cancer study. Methods This is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) for metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) and overall survival, and toxicity. A two-stage design was used. Results Overall, there were 16 evaluable patients. Median age was 68 years (range, 25–81); median number of prior lines of therapy, 2. Nine patients had cutaneous and seven non-cutaneous primary tumors. ORR was 25% (4/16). Sixty per cent of patients (3/5) with primary cutaneous scalp or face tumors attained a confirmed response. Six-month PFS was 38%. Altogether, 75% of patients experienced an adverse event (AE) (at least possibly related to drug) (25% grade 3–4 AE); 68.8%, an immune-related AE (irAE) (2 (12.5%), grade 3 or 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase and diarrhea)). There were no grade 5 toxicities. One of seven patients in whom tumor mutation burden (TMB) was assessed showed a high TMB (24 mutations/mb); that patient achieved a partial response (PR). Two of three patients with PDL1 immunohistochemistry assessed had high PDL1 expression; one achieved a PR. Conclusion The combination of ipilimumab and nivolumab demonstrated an ORR of 25% in angiosarcoma, with three of five patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma. Trial registration number NCT02834013.
Cell therapy strategies for COVID-19: Current approaches and potential applications

Cell therapy has strong promise for treating COVID-19 survivors due to customizability, targetability, and regenerative function. Coronavirus disease 2019 (COVID-19) continues to burden society worldwide. Despite most patients having a mild course, severe presentations have limited treatment options. COVID-19 manifestations extend beyond the lungs and may affect the cardiovascular, nervous, and other organ systems. Current treatments are nonspecific and do not address potential long-term consequences such as pulmonary fibrosis, demyelination, and ischemic organ damage. Cell therapies offer great potential in treating severe COVID-19 presentations due to their customizability and regenerative function. This review summarizes COVID-19 pathogenesis, respective areas where cell therapies have potential, and the ongoing 89 cell therapy trials in COVID-19 as of 1 January 2021.
Psychiatric Nurses’ Lived Experiences of Workplace Violence in Acute Care Psychiatric Units in Western Canada

Abstract Workplace violence directed at nurses in healthcare settings is a common occurrence across the globe resulting in negative nurse and organizational implications that may impact the quality of care provided. Psychiatric nurses working on acute care psychiatric units are at an increased risk and are frequently subjected to patients’ violent and aggressive behaviors. These implications pose significant threats to the nurses’ emotional, physical, and psychological health. Efforts to reduce workplace violence on acute care psychiatric units requires an examination of psychiatric nurses’ lived experiences. A qualitative descriptive phenomenological inquiry was conducted using semi-structured interviews with 10 registered psychiatric nurses within a Western Canada health region to explore their lived experiences of patient-to-nurse workplace violence. The findings of this study highlight the implications of workplace violence and substantiates the urgent need to improve the safety on acute care psychiatric units.
Amphiregulin promotes hair regeneration of skin‐derived precursors via the PI3K and MAPK pathways

There are significant clinical challenges associated with alopecia treatment, including poor efficiency of related drugs and insufficient hair follicles (HFs) for transplantation. Skin‐derived precursors (SKPs) exhibit great potential as stem cell‐based therapies for hair regeneration; however, the proliferation and hair‐inducing capacity of SKPs gradually decrease during culturing.
Tablet‐assisted objective structured spotter practical examination (TOSSPE): Advantages of an innovative anatomy spotter examination method for medical student assessment

The affordances of technology‐based assessments, like the objectively structured practical examination, have become an integral part of gross anatomy courses. The Department of Anatomy Faculty of Medicine at the University of Warmia and Mazury developed and introduced an application for tablet devices which has been implemented in student examinations and assessments, called the tablet‐assisted objective structured spotter practical examination. It was created to simplify the educational process and to build a rich learning environment, facilitating deep learning for students through examination and feedback data. The method consists of cadaver stations with traditional corresponding pin spotters in an expanded tablet application. It not only provides instant feedback on various observations of teaching–learning skills but has also positively affected the entire process of education. The method provides an unbiased evaluation of knowledge and understanding of the anatomy course, ensuring objectivity and standardization. The current study was performed on a total of 608 first‐year medical students in Polish and English divisions and focused on the observed advantages since the new method was introduced. Outcomes indicate that after the implementation of the method for both the Polish and English divisions' first‐year medical students, the mean score of examinations significantly increased compared to other teaching–learning methods. The study highlights that students were excited about the implementation of the new method and identified its many benefits. It is recognized that technological development and the digital environment offer a range of opportunities and added value versus traditional assessment activities, methods, and processes.
The impact of COVID-19 national lockdown on orthopaedic trauma admissions in the northern part of South Africa: A multicentre review of tertiary- and secondary-level hospital admissions.

BACKGROUND COVID-19 national lockdown measures in South Africa (SA) have been under scrutiny since they were implemented in March 2020. Currently there are no studies showing the effect of the first lockdown on hospital admissions in the northern provinces of SA. OBJECTIVES To evaluate the impact of national lockdown restrictions on musculoskeletal injury admissions in three hospitals across three provinces (Gauteng, Limpopo and North West). METHODS In a retrospective review, we compared orthopaedic trauma admissions from 1 April 2020 to 30 June 2020 (during alert level 5 of the national lockdown) with cases admitted during the same period in 2019 (non-lockdown). We reviewed the number of admissions, demographic data and mechanisms of injury in the adult and paediatric population groups. RESULTS A total of 449 patients were admitted with musculoskeletal injuries during the lockdown period compared with 664 patients in 2019, equating to a 32% reduction in total admissions. While there was an 8% increase in paediatric admissions during lockdown at Dr George Mukhari Academic Hospital, adult admissions decreased in all centres. More young males were admitted during both lockdown (mean age 39.8 years) and non-lockdown (mean age 41.2 years) periods than females (p=0.004). There were significant reductions in the number of injuries due to motor vehicle accidents (59%) and in the number of gunshot wounds (36%) during lockdown. However, we observed an 11% rise in injuries related to suicide attempts among adult admissions during the lockdown period. CONCLUSIONS Lockdown restrictions resulted in a significant reduction in orthopaedic trauma admissions, and were effective in terms of allowing institutions to direct resources to the management of COVID-19 patients. In the light of the increased suicide attempts observed during lockdown, future lockdown regulations should include comprehensive measures to relieve socioeconomic stress.
Late Recurrence in a Rectal Cancer Patient Who Underwent Preoperative Chemoradiotherapy Followed by Local Excision: A Case Report

Some patients who have undergone preoperative chemoradiotherapy (CRT) following surgery have been diagnosed with late recurrence more than 5 years after treatment, raising questions about the possible benefit extending surveillance beyond the recommended 5 years. In 2011, a 71-year-old male patient was diagnosed with T3N+ low-lying rectal cancer located 3 cm from the anal verge before undergoing long-course preoperative CRT. After CRT, the patient was reexamined and diagnosed with ycT1–2N0 lesion, so local excision (LE) was performed. The patient underwent intensive surveillance for up to 5 years, and no evidence of recurrence was found. At 74 months after surgery, the patient was hospitalized for a hematochezia, and local recurrence at the excision site and peritoneal seeding nodules were identified. Considering the late recurrence in this patient, it might be necessary to long-term follow-up beyond 5 years in patients with preoperative CRT followed by LE.
Muscle Oxygenation, Neural, and Cardiovascular Responses to Isometric and Workload-matched Dynamic Resistance Exercise

Abstract Differences in blood flow patterns and energy cost between isometric and dynamic resistance exercise may result to variant cardiovascular, neural, and muscle metabolic responses. We aimed to compare the cardiovascular, baroreceptor sensitivity, and muscle oxygenation responses between workload-matched, large muscle-mass isometric and dynamic resistance exercises. Twenty-four young men performed an isometric and a dynamic double leg-press protocol (4 sets×2 min) with similar tension time index (workload). Beat-by-beat hemodynamics, baroreceptor sensitivity, muscle oxygenation, and blood lactate were assessed. The increase in blood pressure was greater (p<0.05) in the 1st set during dynamic than isometric exercise (by ~4.5 mmHg), not different in the 2nd and 3rd sets, and greater in the 4th set during isometric exercise (by ~5 mmHg). Dynamic resistance exercise evoked a greater increase in heart rate, stroke volume, cardiac output, and contractility index (p<0.05), and a greater decline in peripheral resistance, baroreceptor sensitivity, and cardiac function indices than isometric exercise (p<0.05). Participants exhibited a greater reduction in muscle oxyhemoglobin and a greater increase in muscle deoxyhemoglobin in dynamic versus isometric exercise (p<0.001–0.05), with no differences in total hemoglobin and blood lactate. In conclusion, large muscle-mass, multiple-set isometric exercise elicits a relatively similar blood pressure but blunted cardiovascular and baroreceptor sensitivity responses compared to workload-matched dynamic resistance exercise. Differences in blood pressure responses between protocols appear small (~5 mmHg) and are affected by the number of sets. The muscle oxidative stimulus is greater during dynamic resistance exercise than workload-matched isometric exercise.
Cognitive performance of women at various stages of reproductive aging and associated risk factors

Abstract Objective Menopausal transition among midlife women is accompanied by the issues of hot flushes, mood swings as well as sleep disturbances, night sweats, urogenital diminution and cognitive changes. The present cross-sectional study is an attempt to recognize the cognitive differences associated with various stages of reproductive aging. Methods The study included women (N = 404) aged between 40 and 65 years from rural areas of Punjab (North India). The Mini-Mental State Examination (Hindi version) was used to evaluate orientation, registration, attention, recall, language and visual spatial skills domains of the global cognitive functioning of all participants. Results The results of the present study exhibited a decline in cognitive scores across successive menopausal transitional stages in most of the cognitive domains except registration. The results of multivariate regression analysis demonstrated that illiteracy, vegetarian diet, perimenopause and late postmenopause phase were significantly associated with lower global cognitive scores. Conclusion With increased longevity, early identification of potential risk factors associated with cognitive decline among women during their midlife can be beneficial in improving the mental health of postmenopausal women.
Management of Auditory Processing Difficulties Virtually: A Case Study

Abstract Difficulty hearing in the presence of background noise is a common complaint heard by audiologists. This can be accompanied by additional difficulty in classrooms and other difficult listening situations. This was recently exacerbated by the coronavirus disease 2019 (COVID-19) shutdowns and the accompanying mask usage and virtual meetings. This article describes one such patient seen during the recent shutdown. This patient reported difficulty hearing during her college coursework for her music performance major. She was an established otology patient with an extensive middle ear history including multiple surgeries. During the shutdown, she virtually consulted with the auditory processing disorders clinic at the recommendation of her otologist to discuss her college-related difficulty and pursue educational accommodations. Challenges and solutions for seeing this patient and other, similar patients virtually are discussed as well as a review of how this patient proceeded and how the knowledge gained from this patient could apply to others with similar concerns.
Advances and highlights in allergic rhinitis

Allergic rhinitis (AR) is a growing public health, medical and economic problem worldwide. The current review describes the major discoveries related to AR during the past 2 years, including risk factors for the prevalence of AR, the corresponding diagnostic strategy, precise underlying immunological mechanisms, and efficient therapies for AR during the ongoing global “coronavirus disease 2019” (COVID‐19) pandemic. The review further attempts to highlight future research perspectives. Increasing evidence suggests that environmental exposures, climate changes, and lifestyle are important risk factors for AR. Consequently, detailed investigation of the exposome and the connection between environmental exposures and health in the future should provide better risk profiles instead of single predictors, and also help mitigate adverse health outcomes in allergic diseases. Although patients with dual AR, a newly defined AR phenotype, display perennial and seasonal allergens‐related nasal symptoms, they are only allergic to seasonal allergens, indicating the importance of measuring inflammation at the local sites. Herein, we suggest that a combination of precise diagnosis in local sites and traditional diagnostic methods may enhance the precision medicine‐based approach for management of AR; however, this awaits further investigations. Apart from traditional treatments, social distancing, washing hands, and disinfection are also required to better manage AR patients in the ongoing global COVID‐19 pandemic. Despite recent advances in understanding the immune mechanisms underlying the effects of allergen immunotherapy (AIT), further understanding changes of cell profiles after AIT and accurately evaluate the efficacy of AIT are required.
Profiling Human Cytomegalovirus-Specific T Cell Responses Reveals Novel Immunogenic Open Reading Frames

To understand the crucial role of adaptive immunity in controlling cytomegalovirus infection and disease, we systematically analyzed the CMV “ORFeome” to identify new CMV epitopes targeted primarily by CD4 T cells in humans. Our study identified >200 new T cell epitopes derived from both canonical and novel ORFs, highlighting the substantial breadth of the anti-CMV T cell response and providing new targets for vaccine design. ABSTRACT Despite the prevalence and medical significance of human cytomegalovirus (HCMV) infections, a systematic analysis of the targets of T cell recognition in humans that spans the entire genome and includes recently described potential novel open reading frames (ORFs) is not available. Here, we screened a library of epitopes predicted to bind HLA class II that spans over 350 different HCMV ORFs and includes ∼150 previously described and ∼200 recently described potential novel ORFs by using an ex vivo gamma interferon (IFN-γ) FluoroSpot assay. We identified 235 unique HCMV-specific epitopes derived from 100 ORFs, some previously described as immunodominant and others that were not previously described to be immunogenic. Of those, 41 belong to the set of recently reported novel ORFs, thus providing evidence that at least some of these are actually expressed in vivo in humans. These data reveal that the breadth of the human T cell response to HCMV is much greater than previously thought. The ORFs and epitopes identified will help elucidate how T cell immunity relates to HCMV pathogenesis and instruct ongoing HCMV vaccine research. IMPORTANCE To understand the crucial role of adaptive immunity in controlling cytomegalovirus infection and disease, we systematically analyzed the CMV “ORFeome” to identify new CMV epitopes targeted primarily by CD4 T cells in humans. Our study identified >200 new T cell epitopes derived from both canonical and novel ORFs, highlighting the substantial breadth of the anti-CMV T cell response and providing new targets for vaccine design.