bluuebunny/crossref_metadata_2025 huggingface dataset:
Saliva of persons with hemophilia A triggers coagulation via extrinsic tenase complexes
Authors: Thaler Johannes , Tripisciano Carla , Kraemmer Daniel , Hau Chi , Samadi Nazanin , Ruf Wolfram , Pabinger Ingrid , Knoebl Paul , Nieuwland Rienk , Ay Cihan
Published: October 2024

Human saliva contains extracellular vesicles (EVs). These EVs expose extrinsic tenase complexes of tissue factor (TF) and activated factor VII (FVIIa), and trigger blood coagulation. Here, we show that EVs exposing extrinsic tenase complexes are also present in saliva of persons with severe hemophilia A, that is, persons with FVIII deficiency. Addition of these salivary EVs to autologous FVIII-deficient blood results in FXa generation, thereby compensating for the lack of FXa generation via intrinsic tenase (FVIIIa/FIXa) complexes. Consistently, in our retrospective analysis of persons with severe hemophilia A who do not receive prophylactic FVIII substitution, oropharyngeal mucosal bleedings are infrequent and self-limited. Conversely, in saliva of persons with severe FVII deficiency, in whom oropharyngeal bleedings are prevalent, functional extrinsic tenase complexes are absent, because EVs lack FVII. Saliva of persons with severe FVII deficiency is unable to restore blood coagulation, which is because of the absence of FVII in both their saliva and blood. Picomolar levels of recombinant FVIIa can restore the coagulant potential of saliva of persons with FVII deficiency. Taken together, our findings may explain the paucity of oropharyngeal bleedings in persons with hemophilia A as well as the occurrence of such bleedings in persons with severe FVII deficiency.
Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical study
Authors: Antypiuk Ada , Vance S. Zebulon , Sharma Richa , Passos Sara , Asperti Michela , Navaneethabalakrishan Shobana , Dürrenberger Franz , Manolova Vania , Vinchi Francesca
Published: October 2024

Although iron overload is a common feature in myelodysplastic syndromes (MDS), it remains unclear how iron excess is detrimental for disease pathophysiology. Taking advantage of complementary approaches, we analyzed the impact of iron overload and restriction achieved through genetic activation of ferroportin (FPN) via the C326S mutation (FPNC326S) and pharmacologic inhibition (vamifeport) of the iron exporter FPN, respectively, in a MDS mouse model. Although FPNC326S-induced iron overload did not significantly improve the late stages of erythroid maturation, vamifeport-mediated iron restriction ameliorated anemia and red blood cell maturation in MDS mice, through the reduction of oxidative stress and apoptosis in erythroid progenitors. Iron overload aggravated, and restriction alleviated, reactive oxygen species formation, DNA damage, and cell death in hematopoietic stem and progenitor cells (HSPCs), resulting in altered cell survival and quality. Finally, myeloid bias, indicated by expanded bone marrow myeloid progenitors and circulating immature myeloid blasts, was exacerbated by iron excess and attenuated by iron restriction. Overall, vamifeport treatment resulted in improved anemia and significant survival increment in MDS mice. Interestingly, the combined therapy with vamifeport and the erythroid maturation agent luspatercept has superior effect in improving anemia and myeloid bias as compared with single treatments and offers additive beneficial effects in MDS. Our results prove, to our knowledge, for the first time in a preclinical model, that iron plays a pathologic role in transfusion-independent MDS. This is likely aggravated by transfusional iron overload, as suggested by observations in the FPNC326SMDS model. Ultimately, the beneficial effects of pharmacologic FPN inhibition uncovers the therapeutic potential of early prevention of iron toxicity in transfusion-independent MDS.
Can a single question replace patient-reported outcomes in the follow-up of elbow arthroplasty? A validation study
Authors: Macken Arno A. , Prkic Ante , Koenraadt-van Oost Iris , Buijze Geert A. , The Bertram , Eygendaal Denise
Published: October 2024

Background

To assess the results after elbow arthroplasty it is essential to gather patient-reported outcome measures (PROMs). However, the acquisition of PROMs poses a challenge because of potential low literacy, lengthiness and diversity of questionnaires, and questionnaire fatigue. Instead of a questionnaire, patient-reported outcomes can be collected using a single assessment numeric evaluation (SANE), the subjective elbow value (SEV). The aim of this pilot study is to assess the correlation between the SEV and conventionally used patient reported outcome measures (PROMs) after elbow arthroplasty.

Materials and methods

The SEV was added to our follow-up system in 2021, consisting of a scale from 0 to 10 in which the patients are asked to rate the overall functionality of their elbow, 0 corresponds to very poor functionality and 10 to a perfectly functional or healthy elbow. All patients who underwent elbow arthroplasty (total or radial head) and responded to the SEV question were retrospectively identified and included. The correlation between the SEV at the final follow-up and the Oxford Elbow Score (OES), and between the SEV and the Quick Disbailities of the Arm, Shoulder, and Hand (quickDASH) score was assessed using Pearson’s r.

Results

In total, 82 patients responded to the SEV question and were included in the study, with a median follow-up of 5 years [interquartile range (IQR) 3–7]. Of these patients, 17 (21%) underwent radial head arthroplasty and 65 (79%) total elbow arthroplasty. The Pearson’s r for the correlation between SEV and OES was 0.502 (p < 0.001) and between the SEV and the QuickDASH −0.537 (p < 0.001), which correspond to a moderate correlation.

Conclusions

The SEV shows a moderate correlation with conventional PROMs, demonstrating its potential in simplifying the follow-up of elbow arthroplasty, possibly decreasing time, costs, and patients’ questionnaire fatigue compared with conventional PROM questionnaires.

Evidence level: III.
CO2 delivery techniques in mini-sternotomy surgery and neurological events: a multicentric study
Authors: Weltert Luca P. , Audisio Katia , Torre Michele La , Dell’Aquila Michele , Cancelli Gianmarco , Lodo Vittoria , Caldonazo Tulio , Rossi Camilla S. , Soletti Giovanni J. , Garufi Luigi , Centofanti Paolo , De Paulis Ruggero , Rinaldi Mauro
Published: October 2024

Background

The impact of air bubbles into the cerebral circulation after open heart surgery has been a topic of discussion since the introduction of the heart-lung machine. The aim of the study was to evaluate whether the use of a dedicated commercial sponge diffuser is better than a custom-made narrow section cannula or the absence of CO2 in preventing neurological events after aortic valve replacement via J mini-sternotomy.

Methods

Three cohorts of J-shaped mini-sternotomy performed at three different centers were prospectively compared: CO2 supplied via sponge diffuser, CO2 supplied via cannula, and no CO2 supply. Propensity matching was used to obtain comparable groups. The primary endpoints were postoperative stroke, transitory ischemic attack, convulsions, and dizziness. Secondary endpoints were 30-day mortality, duration of mechanical ventilation, and intensive care unit length of stay.

Results

275 patients were enrolled in the study. After propensity matching, the sponge diffuser cohort had a significantly lower duration of mechanical ventilation (P < 0.001) and 30-day mortality (P = 0.05) when compared to the cannula cohort and the no-CO2 cohort, a lower incidence of all neurological events (P = 0.03) and dizziness (P = 0.05) when compare to the no-CO2 cohort, and a lower intensive care unit length of stay when compared to the cannula cohort (P = 0.001).

Conclusions

The sponge diffuser used to deliver the CO2 into the surgical field during aortic valve replacement via J mini-sternotomy has been demonstrated to guarantee better neurological outcomes compared to a custom-made narrow section cannula or the absence of CO2.
Qualitative drivers of postoperative prophylactic antibiotics use and resistance in Ethiopia
Authors: Steeman Samantha , Nofal Maia R. , Heyredin Ibrahim , Asmamaw Hailemichael , Tesfaye Assefa , Zhuang Alex , Gebeyehu Natnael , Merrell Sylvia Bereknyei , Weiser Thomas G. , Mammo Tihitena Negussie
Published: October 2024

Background

The World Health Organization (WHO) cautions against unnecessary prolongation of postoperative antibiotics to prevent surgical site infections (SSI), however this practice is still common in many countries. This study aims to describe drivers of prolonged postoperative antibiotic prescribing and clinicians’ perspectives on antibiotics resistance and stewardship in Ethiopia.

Methods

We conducted semi-structured interviews of 16 surgeons and nine surgical ward nurses at three academic referral hospitals in Addis Ababa. Audio recordings were transcribed verbatim and coded. Codes were inductively and iteratively derived between two researchers, tested for inter-rater reliability (IRR), and the codebook was consistently applied to all transcripts. Thematic analysis was performed to understand drivers of prolonged prophylactic antibiotic use in surgical patients.

Results

Interviews revealed factors contributing to postoperative prophylactic antibiotics overprescribing, including inadequate infection prevention and control (IPC) practices, wide variability in local prescribing practices, and distrust in the applicability of WHO guidelines. Antimicrobial resistance was also identified as a major concern by staff. Barriers to improving stewardship included a lack of multidisciplinary teamwork to inform prescribing decisions, while solutions included constructing appropriate context-specific guidelines and improving evidence-based practices through input from local stakeholders, including surgeons, clinical pharmacists, and nurses.

Conclusions

Study participants perceived that existing evidence and guidelines did not apply in their settings due to high rates of surgical site infections and gaps in perioperative IPC practices (e.g., availability of water for handwashing, sterility breaches). These gaps were a key contributor to prophylactic antibiotic overprescribing, reinforcing the need to strengthen upstream and perioperative surgical antisepsis processes. The findings of this study underscore the importance of engaging multidisciplinary teams in strengthening antimicrobial stewardship efforts, aligning processes to achieve compliance with best practices, and the need for rigorous, contextually appropriate studies from these settings to inform policy.
Ultrastructural characterization of hippocampal inhibitory synapses under resting and stimulated conditions
Authors: Tao-Cheng Jung-Hwa , Moreira Sandra Lara , Winters Christine A.
Published: October 2024

The present study uses electron microscopy to document ultrastructural characteristics of hippocampal GABAergic inhibitory synapses under resting and stimulated conditions in three experimental systems. Synaptic profiles were sampled from stratum pyramidale and radiatum of the CA1 region from (1) perfusion fixed mouse brains, (2) immersion fixed rat organotypic slice cultures, and from (3) rat dissociated hippocampal cultures of mixed cell types. Synapses were stimulated in the brain by a 5 min delay in perfusion fixation to trigger an ischemia-like excitatory condition, and by treating the two culture systems with 90 mM high K+ for 2–3 min to depolarize the neurons. Upon such stimulation conditions, the presynaptic terminals of the inhibitory synapses exhibited similar structural changes to those seen in glutamatergic excitatory synapses, with depletion of synaptic vesicles, increase of clathrin-coated vesicles and appearance of synaptic spinules. However, in contrast to excitatory synapses, no structural differences were detected in the postsynaptic compartment of the inhibitory synapses upon stimulation. There were no changes in the appearance of material associated with the postsynaptic membrane or the length and curvature of the membrane. Also no change was detected in the labeling density of gephyrin, a GABAergic synaptic marker, lining the postsynaptic membrane. Furthermore, virtually all inhibitory synaptic clefts remained rigidly apposed, unlike in the case of excitatory synapses where ~ 20–30% of cleft edges were open upon stimulation, presumably to facilitate the clearance of neurotransmitters from the cleft. The fact that no open clefts were induced in inhibitory synapses upon stimulation suggests that inhibitory input may not need to be toned down under these conditions. On the other hand, similar to excitatory synapse, EGTA (a calcium chelator) induced open clefts in ~ 18% of inhibitory synaptic cleft edges, presumably disrupting similar calcium-dependent trans-synaptic bridges in both types of synapses.
Telehealth-delivered cognitive rehabilitation for people with cognitive impairment as part of the post-COVID syndrome: protocol for a randomised controlled trial as part of the CICERO (Cognitive Impairment in Long COVID: Phenotyping and Rehabilitation) study
Authors: Vanova Martina , Patel Aysha Mohamed Rafik , Scott Iona , Gilpin Gina , Manning Emily N. , Ash Charlotte , Wittenberg Philippa , Lim Jason , Hoare Zoe , Evans Rachel , Bray Nathan , Kipps Christopher M. , Devine Ciara , Ahmed Saliha , Dunne Ross , Koniotes Anna , Warren Catherine , Chan Dennis , Suarez-Gonzalez Aida
Published: October 2024

Background

Between 25 and 75% of people with persistent post-acute sequelae of SARS-CoV-2 infection (PASC) experience cognitive difficulties, compromising functional ability, quality of life, and activities of daily living, including work. Despite this significant morbidity, there is a paucity of interventions for this disorder that have undergone evaluation within a formal trial setting. Therefore, we have developed a cognitive rehabilitation programme, specifically designed to address the cognitive symptoms of PASC, notably impaired attention and processing speed, while also accounting for other PASC symptoms (fatigue, post-exertional malaise) that may aggravate the cognitive impairment. This study protocol outlines a randomised controlled trial (RCT) designed to evaluate the effectiveness of this programme compared to standard clinical care.

Methods

This is a multi-centre, parallel-group, individually randomised controlled trial, comparing standard clinical care with and without cognitive rehabilitation. We will recruit 120 non-hospitalised adults (aged 30–60 years) from three NHS sites in England with a history of COVID-19 infection and cognitive impairment persisting more than 3 months after the acute infection. Participants will be randomised (1:1) to the intervention or control groups, with the latter represented as a provision of standard clinical care without cognitive rehabilitation. The cognitive rehabilitation programme consists of ten 1-hour sessions, delivered weekly. Outcomes will be collected at baseline, 3, and 6 months, with participant-defined goal-attainment scores, relating to functional goals, at 3 months as the primary outcome measure. Secondary outcomes will be cognitive function, measures of quality of life, social functioning, mental health, fatigue, sleep, post-exertional malaise, and social and health care service use. We will also evaluate the health-economic benefits of cognitive rehabilitation in this population.

Discussion

Cognitive impairment in PASC is a major cause of functional disability with no effective treatment. Accordingly, we will undertake an RCT of cognitive rehabilitation, the protocol of which is published here. If this trial is successful in delivering improvements in trial outcomes, it will address a major unmet need relating to this emergent disorder, with a significant impact on affected individuals and the wider health economy.

Trial registration

ClinicalTrials.gov NCT05731570. Registered on February 16, 2023
Pathological mechanisms and candidate therapeutic approaches in the hearing loss of mice carrying human MIR96 mutations
Authors: Lewis Morag A. , Lachgar-Ruiz Maria , Di Domenico Francesca , Duddy Graham , Chen Jing , Fernandez Sergio , Morin Matias , Williams Gareth , Moreno Pelayo Miguel Angel , Steel Karen P.
Published: October 2024

Background

Progressive hearing loss is a common problem in the human population with no effective therapeutics currently available. However, it has a strong genetic contribution, and investigating the genes and regulatory interactions underlying hearing loss offers the possibility of identifying therapeutic candidates. Mutations in regulatory genes are particularly useful for this, and an example is the microRNA miR-96, a post-transcriptional regulator which controls hair cell maturation. Mice and humans carrying mutations in miR-96 all exhibit hearing impairment, in homozygosis if not in heterozygosis, but different mutations result in different physiological, structural and transcriptional phenotypes.

Methods

Here we present our characterisation of two lines of mice carrying different human mutations knocked-in to Mir96. We have carried out auditory brainstem response tests to examine their hearing with age and after noise exposure and have used confocal and scanning electron microscopy to examine the ultrastructure of the organ of Corti and hair cell synapses. Bulk RNA-seq was carried out on the organs of Corti of postnatal mice, followed by bioinformatic analyses to identify candidate targets.

Results

While mice homozygous for either mutation are profoundly deaf from 2 weeks old, the heterozygous phenotypes differ markedly, with only one mutation resulting in hearing impairment in heterozygosis. Investigations of the structural phenotype showed that one mutation appears to lead to synaptic defects, while the other has a much more severe effect on the hair cell stereociliary bundles. Transcriptome analyses revealed a wide range of misregulated genes in both mutants which were notably dissimilar. We used the transcriptome analyses to investigate candidate therapeutics, and tested one, finding that it delayed the progression of hearing loss in heterozygous mice.

Conclusions

Our work adds further support for the importance of the gain of novel targets in microRNA mutants and offers a proof of concept for the identification of pharmacological interventions to maintain hearing.
The influence of sex on neuroimmune communication, pain, and physiology
Authors: Alexander Shevon N. , Green Audrey R. , Debner Emily K. , Ramos Freitas Lindsey E. , Abdelhadi Hanna M. K. , Szabo-Pardi Thomas A. , Burton Michael D.
Published: October 2024

With the National Institutes of Health’s mandate to consider sex as a biological variable (SABV), there has been a significant increase of studies utilizing both sexes. Historically, we have known that biological sex and hormones influence immunological processes and now studies focusing on interactions between the immune, endocrine, and nervous systems are revealing sex differences that influence pain behavior and various molecular and biochemical processes. Neuroendocrine-immune interactions represent a key integrative discipline that will reveal critical processes in each field as it pertains to novel mechanisms in sex differences and necessary therapeutics. Here we appraise preclinical and clinical literature to discuss these interactions and key pathways that drive cell- and sex-specific differences in immunity, pain, and physiology.
Balancing the encoder and decoder complexity in image compression for classification
Authors: Duan Zhihao , Hossain Md Adnan Faisal , He Jiangpeng , Zhu Fengqing
Published: October 2024

This paper presents a study on the computational complexity of coding for machines, with a focus on image coding for classification. We first conduct a comprehensive set of experiments to analyze the size of the encoder (which encodes images to bitstreams), the size of the decoder (which decodes bitstreams and predicts class labels), and their impact on the rate–accuracy trade-off in compression for classification. Through empirical investigation, we demonstrate a complementary relationship between the encoder size and the decoder size, i.e., it is better to employ a large encoder with a small decoder and vice versa. Motivated by this relationship, we introduce a feature compression-based method for efficient image compression for classification. By compressing features at various layers of a neural network-based image classification model, our method achieves adjustable rate, accuracy, and encoder (or decoder) size using a single model. Experimental results on ImageNet classification show that our method achieves competitive results with existing methods while being much more flexible. The code will be made publicly available.
Age at first sex and other determinants of multiple sexual partnerships among sexually active adolescent girls in Ghana: a regression analysis of the 2022 Ghana demographic and health survey
Authors: Klu Desmond , Odame Micheal Larbi , Acquah Evelyn , Dansu Charity Akpene
Published: October 2024

Background

Early sexual debut is a widely recognized public health issue due to its influence on lifetime multiple sexual partners which can lead to complications such as teenage pregnancy, abortion, HIV/AIDS and other sexually transmitted infections. However, there is paucity of research evidence on sexual behaviour such as age at first sexual intercourse and the number of sexual partnerships among adolescent girls in Ghana. This study aims to examine the influence of age at first sexual intercourse and other determinants on multiple sexual partnerships among adolescent girls aged 15–19 years in Ghana.

Methods

Data for this study were obtained from the 2022 Ghana Demographic and Health Survey (GDHS) conducted between October 17, 2022 and January 14, 2023. A total weighted sample of 719 sexually active adolescent girls who reported having sexual partners was extracted from the women’s data file. Data were analyzed with SPSS version 27, employing multilevel logistics regression modelling. Statistical significance was set at p < 0.05.

Results

The average age at sexual debut for adolescent girls aged 15–19 years in Ghana is 15.5 years. A little over half (51.6%) of adolescent girls reported having two or more lifetime sexual partners. Adolescent girls who initiated sex before reaching age 15 were more likely (aOR = 2.00; C.I 1.39–2.87) to have multiple partners compared to those who had their first sex before attaining age 20. After controlling for other factors, girls who had their sexual debut before age 15 had higher odds (aOR = 1.85; C.I:1.30–3.31) of engaging in multiple sexual partnerships. Girls living female headed households (aOR = 2.25; C.I:1.18–4.29] and consuming alcohol (aOR = 2.38; C.I 2.38–1.09–5.17) had higher odds of having multiple sexual partners.

Conclusion

The study findings show that early sexual debut, living in female headed household, and consuming alcohol are strong predictors of multiple sexual partnerships among adolescent girls in Ghana. It suggests the need for policies promoting delayed sexual debut and empowering adolescents to make informed decisions to improve sexual health outcomes.
DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish
Authors: Klempner Samuel J. , Sonbol Mohamad Bassam , Wainberg Zev A. , Uronis Hope Elizabeth , Chiu Vi K. , Scott Aaron James , Iqbal Syma , Tejani Mohamedtaki Abdulaziz , Chung Vincent , Stilian Melissa C. , Thoma Mathis , Zhang Ying , Kagey Michael H. , Baum Jason , Sirard Cynthia A. , Altura Rachel A. , Ajani Jaffer A.
Published: October 2024

PURPOSE

The outcomes of anti–PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study.

PATIENTS AND METHODS

Patients had untreated human epidermal growth factor receptor 2–negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m
2
once every 3 weeks, and capecitabine 1,000 mg/m
2
twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS).

RESULTS

Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%.

CONCLUSION

DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier:
NCT04363801
).
Do regular quantum black holes exist?
Authors: Singh Harpreet , Nandy Malay K.
Published: October 2024

Regular black holes do not exist in any classical theory of gravity including Einstein's general relativity. This unappealing feature is due to the appearance of a singularity in the interior of the black hole described by any classical theory. As Hawking argued, all known laws of physics must break down at the singularity. It is thus an important question whether this singularity can disappear in a quantum mechanical description of spacetime. In this letter, we therefore quantize the black hole interior in a Kantowski-Sachs minisuperspace representation in the presence of spontaneous Klein-Gordon matter field fluctuations. This leads to a Wheeler-DeWitt equation whose solution yields the interior wave function of the black hole. The regular part of this wave function satisfies the DeWitt boundary condition in that it vanishes at the singularity. Moreover, the wave function is regular and well behaved in the region around the singularity. These features of the wave function suggest that regular black holes do exist in quantum gravity.
Degradation of coral reef ecosystems: Mathematical-dynamical modeling approach
Authors: Zhao Xin , Yu Shiyang , Fan Meng
Published: October 2024

This paper delves into the frontier of degradation of coral reef ecosystems, a pressing urgent issue to be addressed given the escalating threats faced by the crucial marine environments, and provides a critical assessment of recent advances, emerging trends, and valuable perspective on the studies employing mathematical-dynamical modeling approaches. This study highlights the recent developments in coral bleaching, coral-algal phase shifts, coral disease, and natural enemy bloom, all of which are thoroughly documented and comprehensively expounded. This review study also offers some valuable insights, illuminating ideas, and clear perspective into some current, emerging, and promising research directions for future studies, particularly those based on mathematical and biological modeling. These approaches are anticipated to offer a robust theoretical framework and provide crucial decision-making reference for the protection, restoration, and management of coral reef ecosystems.
Three Siblings With Familial Isolated Hypoparathyroidism: A Diagnostic Journey From CASR to Novel GCM2 Variant
Authors: Thambundit Apisadaporn , Martinez-Agosto Julian A , Kianmahd Shamshoni Jessica , Winer Karen K , Mittelman Steven D
Published: October 2024

We report a patient who initially presented at 4 days old with hypocalcemia, hypoparathyroidism, and elevated phosphorous level. Treatment was initiated with calcitriol, calcium carbonate (CaCO3), vitamin D, and low phosphorous formula. Family history was positive for an activating calcium sensing receptor (CASR) variant (R990G) identified previously in 2 older siblings who were treated with CaCO3 and calcitriol. However, genetic studies were negative for the CASR variant in our patient. She maintained a large calcium requirement and was admitted for multiple episodes of hypocalcemia. Further investigation revealed that the CASR variant identified in the older siblings was now considered a benign, nondisease-causing variant. Whole exome sequencing on our proband revealed a homozygous pathogenic variant in the GCM2 gene (Gln392*) consistent with a molecular diagnosis of familial isolated hypoparathyroidism. Genetic studies revealed the 2 older siblings harbor the same genetic changes and parents are heterozygous carriers for this allele. Due to persistent hypocalcemia, we initiated teriparatide. She weaned off calcitriol and achieved normocalcemia on teriparatide, CaCO3, and vitamin D. Siblings transitioned to the same treatment without complications. These findings demonstrate the importance of adequate diagnostic genetic testing and the role of variant reanalysis over time in promoting accurate diagnoses.
Communal Intimacies
Authors: Esparza René
Published: October 2024

The reproduction of the American home hinges on a clear public/private distinction, wherein the private sphere is traditionally viewed as domestic — a space for interpersonal care and social reproduction, distinct from the abstract political culture of the public. Due to American legal and cultural norms maintaining this division, the mainstream LGBTQ rights movement has privileged privacy as a portal of legitimation, often to the detriment of poor, queer people of color without access to private property. Amid residential segregation, mass incarceration, and welfare reform, queer people of color must reshape and repurpose both public and commercial space to collectively affirm their erotic desires and care for each other through “communal intimacies,” the spatial-kinship practices that decouple care from the domestic, create a pathway for the transfer of libidinal pleasures, and act as a foundation for envisioning and enacting a world of belonging and transformation despite gentrification. Through cultural analysis of John Leguizamo's performance of the “Manny the Fanny” character from his 1991 show Mambo Mouth and Sean Baker's 2015 film Tangerine, this article illustrates novel forms of homemaking that blur the boundaries denoting the public/private spatial divide inherent in neoliberal property regimes.
Knowledge of misconduct amid North-African post-graduate dental students: A cross sectional study
Authors: Kallala Rim , Khemiss Mehdi , Azzouzi Ines , Gassara Yosra , Touzi Soumaya , Harzallah Belhassen , Ben Saad Helmi
Published: October 2024

Background Misconduct in the academic community remains poorly understood among post-graduate dental students (PGDSs) in North Africa. Data on the knowledge of misconduct (KoM) level in this population is lacking. This study assessed KoM of Tunisian PGDSs’. Methods A cross-sectional study was conducted at the Faculty of Dental Medicine of Monastir, involving 147 PGDSs registered in 2022. Students were recruited via email invitations and convenience sampling at a medical congress. A French survey with 11 questions on KoM, offering three-choice answers (yes/no/maybe) was administered. Each correct answer received one point, and a total score below six indicated a low-level of KoM. Results The mean±SD KoM score of the 106 students who accepted to participate in the study was 4.4±1.8, indicating a low-level of KoM. The majority of PGDSs (85.85%) demonstrated a low-level of KoM. A comparison between subjective and objective assessments of KoM levels revealed that a significant percentage of PGDSs underestimated their knowledge (62.26% vs. 85.85%, respectively). The two groups of PGDSs with low (n=91) and acceptable or excellent (n=15) KoM levels showed comparable characteristics in terms of age, sex, discipline, post-graduate-level, experience-level, graduation-status, and survey-response modality. Conclusion This study identified a low-level of KoM among North-African PGDSs. This emphasizes the need for further efforts to enhance awareness and promote better KoM in this population.
SCUBA implements a storage format-agnostic API for single-cell data access in R
Authors: Showers William M. , Desai Jairav , Engel Krysta L. , Smith Clayton , Jordan Craig T. , Gillen Austin E.
Published: October 2024

While robust tools exist for the analysis of single-cell datasets in both Python and R, interoperability is limited, and analysis tools generally only accept one object class. Considerable programming expertise is required to integrate tools across package ecosystems into a comprehensive analysis, due to their differing languages and internal data structures. This complicates validation of results and leads to inconsistent visualizations between analysis suites. Conversion between object formats is the most common solution, but this is difficult and error-prone due to the rapid pace of development of the analysis suites and their underlying data structures. To address this, we created SCUBA (Single-Cell Unified Backend API), an R package that implements a unified data access API for all common R and Python single-cell object formats. SCUBA extends the data access approach from the widely used Seurat package to SingleCellExperiment and anndata objects. SCUBA also implements new data-specific access functions for all supported object types. Performance scales well across all SCUBA-supported formats. In addition to performance, SCUBA offers several advantages over object conversion for the visualization and further analysis of pre-processed single-cell data. First, SCUBA extracts only data required for the operation at hand, leaving the original object unmodified. This process is simpler, less error prone, and less memory intensive than object conversion, which operates on the entire dataset. Second, code written with SCUBA can use any supported object class as input, with simple and consistent syntax across object formats. This allows a single analysis script or package (like our interactive single-cell browser, scExploreR) to work seamlessly with multiple object types, reducing the complexity of the code and improving both readability and reproducibility. Adoption of SCUBA will ultimately improve collaboration and reproducible research in single-cell analysis by lowering the barriers between package ecosystems.
Case Report: Placental site trophoblastic tumor revealed by a clinical pelvic abscess
Authors: Nesrine Souayeh , Bettaieb Hajer , Mbarki Wael , Ehsen Ben Brahim , Imen Helal , Mehdi Ben Nasr , Hedhili Oueslati , Najeh Hsayaoui , Mbarki Chaouki
Published: October 2024

We report an uncommon clinical presentation of a placental site trophoblastic tumor. The patient presented initially with abdominal pain with, fever, bleeding and pelvic mass on ultrasonography leading to the wrong diagnosis of a pelvic abscess. Dilation and curettage were performed and pathological examination confirmed the diagnosis of placental site trophoblastic tumor. Therefore, she underwent abdominal hysterectomy. Four years after surgery, the patient is still disease free. Gestational trophoblastic diseases should be considered in every patient presenting abnormal uterine bleeding after delivery or pregnancy loss despite the associated symptoms being very unusual.
Guidelines for Integrating actionable A-SMART Learning Outcomes into the Backward Design Process
Authors: Kiyan Tsunami Carlos , Henríquez-Trujillo Aquiles Rodrigo , Ferreira-Meyers Karen , Mwanda Ziyanda , Rimal Jyostna , Pozu-Franco Jamine , Delvaux Thérèse , Sibongwere Deogratias Katsuva , Montalvo Navarrete Héctor Javier , Dasgupta Anuttama , Kolie Jean Michel , Luakanda-Ndelemo Gradi , Semevo Claude T. , Heng Sotheara Heng , Dierickx Susan , Kannan Diljtih , Hn Harish , Fucay Guin Luis , Vysyaraju Kranthi , Zolfo Maria
Published: October 2024

Background Learning outcomes are essential in education, guiding both educators and learners towards desired knowledge, skills, and competencies. The backward design process offers a structured approach to curriculum planning, but its integration with actionable, SMART (Specific, Measurable, Achievable, Relevant, Time-bound) learning outcomes needs further exploration. Goal This guide aims to introduce the concept of "A-SMART" learning outcomes and demonstrate their integration into the backward design process, focusing on outcomes that begin with action verbs. Methods The guide outlines a three-stage curriculum planning approach: (i) define desired results, (ii) determine acceptable evidence of learning, and (iii) plan learning activities. It emphasizes the importance of starting with action verbs in formulating learning outcomes, aligning with Stage 1 of backward design and facilitating the transition to Stage 2 (assessment development). Results By following this guide, educators will acquire tools to develop effective "A-SMART" learning outcomes. This approach immediately advances to Stage 2 of backward design, improving educational practices and ensuring alignment with assessment methods. The guide provides strategies for formulating outcomes that are Action-oriented, Specific, Measurable, Achievable, Relevant, and Time-based. Conclusions The integration of A-SMART learning outcomes into the backward design process offers a more cohesive and effective educational framework. This approach enhances clarity for learners, provides guidance for instructors, enables more effective assessments, and improves overall learning experiences. The guide also addresses potential challenges in formulating A-SMART outcomes and suggests solutions, including the use of AI tools for inspiration and critical review.
Twelve Tips for Engaging Medical Students in Rural-Focused Research
Authors: Perez Grace , Perez Jose Uriel , Johnston Aaron
Published: October 2024

Background The future of rural healthcare depends on training the future rural health workforce, and on rural health research that can guide clinical and policy decisions in rural spaces. Promotion of rural healthcare careers usually focuses on clinical aspects of care, and research may be seen as a lower priority. Supporting students to be involved in rural focused research offers the opportunity to broaden the pool of potentially rural interested students, and to develop research and scholarship skills and capacity in the future rural workforce. Aim and method We identify twelve tips that medical schools can adopt to foster medical student participation in research and promote student interest in rural healthcare and rural medical practice. These recommendations are based on a review of literature and our personal experience of conducting rural-focused research activities with medical students. Conclusion Through these twelve tips, we provide a practical framework for enhancing undergraduate medical student exposure to rural-focused research to foster research capacity. This has potential to inspire student interest in future rural medical practice and could contribute to alleviate workforce and research gaps in rural areas.
Letnia stratyfikacja termiczna wody w jeziorach na Niżu Polskim
Authors: Skowron Rajmund
Published: October 2024

Rajmund Skowron collected the most interesting and significant results of his research and analyses. The material query concerned two types of data: 1) stationary measurements of surface water temperature (in this respect, daily water temperatures were collected for 12 lakes in the period 1961–2020); 2) expeditionary measurements of vertical temperature distribution in 715 lakes in the Polish Lowlands during the same period, in large part taken by the author. The longest series of data on water temperature in lakes became the basis for the analysis and the presented conclusions. The author […] performed a thorough analysis of the measurements, presenting the average parameters of the thermal structure of water. On their basis, he distinguished thermal seasons in Polish lakes. Chapter 7 is an attempt at synthesis, in which he analyses long-term changes in water temperature and determines their trends. Particularly valuable content is presented in Chapter 9, which discusses the theses and conclusions contained in European and world literature. The work, using rich documentary material, comprehensively and extensively presents the course of thermal phenomena and processes in lakes in Poland. It will certainly be an important book for a wide range of limnologists of various specialties and will fill the gap in knowledge in this field.
Ziemia. Planeta życia
Authors: Kopcewicz Jan , Sadurski Andrzej , Strobel Andrzej
Published: October 2024

The Earth is a fascinating, unique planet that has gone through different phases of its development over the course of 4.5 billion years. The book presents the particular stages of the formation of the Solar System, the formation of planets and the internal and external structure of the Earth. The geological and biological history of our planet is also described. The factor that determined the Earth’s unique rank is the existence of life on it. The book provides the characteristics of life and the mechanisms of its origin and development. Seventy thousand years ago, Homo sapiens was an insignificant species living in a certain corner of Africa. Over the next millennia, he grew to become the master of the entire planet and the terror of the biosphere. Man has the means and possibilities to both destroy life and cause its spectacular development.  The book includes the description of the history of human civilisation, its current problems and the future of life on our planet and – possibly – beyond it.
Analiza i krytyka Konwencji w sprawie niewolnictwa z dnia 25 września 1926 roku w polskiej myśli polityczno-prawnej doby dwudziestolecia międzywojennego
Authors: Baranowska Marta , Fiktus Paweł
Published: October 2024

Przedmiotem badawczym artykułu jest analiza uwag polskich prawników i przedstawicieli Ministerstwa Spraw Zagranicznych dotyczących Konwencji w sprawie niewolnictwa z 1926 roku. Ze względu na brak kolonii problem niewolnictwa w Polsce był traktowany jako zagadnienie czysto teoretyczne. W artykule omówiono wypowiedzi czołowych polskich prawników, między innymi profesorów Ludwika Ehrlicha i Juliana Makowskiego.
Czeski los
Authors: Kaliski Bartosz
Published: October 2024

Celem tekstu jest przedstawienie doświadczeń pozbawienia wolności czeskiego dziennikarza, dysydenta, obrońcy praw człowieka Jiříego Lederera (1922–1983), związanego od młodości z ruchem socjalistycznym. Lederer w czasie II wojny światowej pracował przymusowo dla III Rzeszy. W okresie stalinizmu przez kilka lat wykonywał prace fizyczne. W latach 1970, 1972 i 1977–1980 zaznał represji: był więźniem politycznym, następnie emigrował do Niemiec Zachodnich.
Polityka władz polskich po 1945 roku w odniesieniu do zbiorów muzealnych. Przykład pozaeuropejskiej kolekcji Państwowego Muzeum Etnograficznego w Warszawie
Authors: Skwirowska Marta
Published: October 2024

Państwowe Muzeum Etnograficzne w Warszawie swoją kolekcję budowało dwukrotnie. Pierwszy etap to okres od 1888 roku, daty założenia Muzeum do wybuchu II wojny światowej. Na przestrzeni 40 lat swojego istnienia Muzeum zgromadziło ok. 30.000 obiektów. Wraz z wybuchem wojny i w wyniku zniszczeń spowodowanych przez okupanta, budynek Muzeum i cała jego zawartość – kolekcje etnografii polskiej, europejskiej i pozaeuropejskiej, a także przedwojenne inwentarze, katalogi, archiwalia i zbiory ikonograficzne – uległy zniszczeniu, rozproszeniu lub zaginięciu.
Po zakończeniu II wojny światowej, środowisko muzealne szybko przystąpiło do odbudowywania sieci muzeów i ich zbiorów, również pracownicy nowopowstałego Muzeum Kultur Ludowych. Dla Muzeum to drugi okres budowania kolekcji od podstaw, tym razem w nowej rzeczywistości Polski Ludowej, kiedy to polityka państwa w dziedzinie muzealnictwa opierała się na tzw. „akcji planowej”. Miała ona na względzie nie tylko uregulowanie sieci muzeów w województwach, lecz również „swobodną dyspozycję” wszystkimi zbiorami muzealnymi na terenie całego kraju. Operacja scalania, re-lokalizacji i centralizacji zbiorów, tak dobitna na przykładzie Muzeum Kultur Ludowych, odzwierciedlała myśl polityczną o muzealnictwie w Polsce w okresie stalinowskim.
Gra w edukację. Konteksty muzealnej działalności edukacyjnej
Authors: Kwiatkowska Olga
Published: October 2024

Artykuł stanowi refleksję etnolożki pracującej jako edukatorka muzealna nad fenomenem edukacji muzealnej. Prezentuje jak ta praktyka kulturowa uwikłana jest w skomplikowane otoczenie, w którym funkcjonuje. Pokazuje jacy społeczni aktorzy jawni, ale też niejawni, są zaangażowani w jej kształtowanie, jak ją definiują, jakie mają wobec niej oczekiwania, jakie padają deklaracje w tym zakresie i jak one się mają do realnych strategii wobec i w muzealnej edukacji.
Trauma and the Museum Exhibition: How to Create an Exhibition on Traumatic Experiences?
Authors: Mosiej-Zambrano Karolina
Published: October 2024

In the article, the author presents the solutions used during the arrangement of the first temporary exhibition of the Sybir Memorial Museum [Memorial Museum Siberia], entitled ‘Only Pain is Mine’, which presents various aspects of the reality of women and girls - their tragic experiences of deportation, exile, imprisonment in the Soviet Union or during the Soviet occupation, mainly in the context of broadly understood femininity, women's bodies and their roles. The article discusses the issue of working with the themes of trauma, traumatization and violence against women addressed in activities carried out during exhibition and education projects.
Uwięzieni przodkowie czy eksponaty? NAGPRA i amerykańskie muzea
Authors: Dżurak Ewa
Published: October 2024

Tekst jest wprowadzeniem do problematyki okoliczności, w jakich doszło do uchwalenia w 1990 r.oku Ustawy o ochronie i repatriacji grobów rdzennych Amerykanów (Native American Grave Protection and Repatriation Act  - NAGPRA), a także samego procesu wdrażania tego prawa. Autorka charakteryzuje sposoby dawnego traktowania artefaktów kultur rdzennych Amerykanów, które przyczyniły się ostatecznie do protestów organizowanych przez grupy rdzennej ludności Ameryki oraz organizacje broniące ich praw do ochrony szkieletowych szczątków przodków oraz dorobku ich kultur. Wskazuje, że działania te ostatecznie doprowadziły do ​​zatwierdzenia ustawy - NAGPRA. W imię jej zasad, muzea, organizacje lub kolekcje, które otrzymują jakikolwiek rodzaj finansowania federalnego, są zobowiązane do tworzenia inwentarzy swoich kolekcji plemiennych, w szczególności wykazów szczątków ludzkich i zwracania ich właścicielom, w celu umożliwienia właściwego pochówku. NAGPRA obejmuje ochroną nie tylko szczątki ludzkie, ale także obiekty religijne i inne przedmioty o przypisanej wielkiej wartości kulturowej. Muszą być one zwrócone poszczególnym grupom na ich żądanie. Przez ostatnie 30 lat muzea na terenie całych Stanów Zjednoczonych reagowały na to prawo dość powoli i wiele artefaktów chronionych na mocy NAGPRA było nadal eksponowanych w rozmaitych kolekcjach. W styczniu 2023 r. wprowadzono kolejne przepisy mające na celu przyspieszenie procesu przestrzegania NAGPRA. Ustalają one bardziej rygorystyczne terminy i dają rdzennym ekspertom większe uprawnienia w zakresie oceny znaczenia, proweniencji i wartości obiektów. Muzea zobowiązano też do zakończenia swoich inwentaryzacji przed 2029 r. Nowe przepisy spowodowały zamknięcie wielu wystaw publicznych i zmianę sposobów współpracy między grupami rdzennej ludności a poszczególnymi muzeami.