bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of aging on the formation and growth of colonic epithelial organoids by changes in cell cycle arrest through TGF-β-Smad3 signaling
Authors: Jo Min Kyoung , Moon Chang Mo , Jeon Hyeon-Jeong , Han Yerim , Lee Eun Sook , Kwon Ji-Hee , Yang Kyung-Min , Ahn Young-Ho , Kim Seong-Eun , Jung Sung-Ae , Kim Tae Il 
Published: July 2023

Abstract
Background
This study aimed to investigate how aging alters the homeostasis of the colonic intestinal epithelium and regeneration after tissue injury using organoid models and to identify its underlying molecular mechanism.

Methods
To investigate aging-related changes in the colonic intestinal epithelium, we conducted organoid cultures from old (older than 80 weeks) and young (6–10 weeks) mice and compared the number and size of organoids at day 5 of passage 0 and the growth rate of organoids between the two groups.

Results
The number and size of organoids from old mice was significantly lower than that from young mice (p < 0.0001) at day 5 of passage 0. The growth rate of old-mouse organoids from day 4 to 5 of passage 0 was significantly slower than that of young-mouse organoids (2.21 times vs. 1.16 times, p < 0.001). RNA sequencing showed that TGF-β- and cell cycle-associated genes were associated with the aging effect. With regard to mRNA and protein levels, Smad3 and p-Smad3 in the old-mouse organoids were markedly increased compared with those in the young-mouse organoids. Decreased expression of ID1, increased expression of p16INK4a, and increased cell cycle arrest were observed in the old mouse-organoids. Treatment with SB431542, a type I TGF-β receptor inhibitor, significantly increased the formation and growth of old-mouse organoids, and TGF-β1 treatment markedly suppressed the formation of young-mouse organoids. In the acute dextran sulfate sodium-colitis model and its organoid experiments, the colonic epithelial regeneration after tissue injury in old mice was significantly decreased compared with young mice.

Conclusions
Aging reduced the formation ability and growth rate of colonic epithelial organoids by increasing cell cycle arrest through TGF-β-Smad3-p16INK4a signaling.
Limited Joint Mobility in Type 1 Diabetes: Diabetic Cheiroarthropathy, a Neglected Entity
Authors: Swain Jayshree , Teli Brij , Sahoo Abhay , Kasukurti Lavanya 
Published: July 2023

Abstract
Musculoskeletal disorders are common in type 1 and type 2 diabetes mellitus. Among them, diabetic cheiroarthropathy (DCA), more commonly seen in type 1 diabetes, is a late complication that often causes physical and emotional disturbance. DCA, characterized by movement restrictions in the small joints of hands, is usually a clinical diagnosis and bears significance owing to the functional hand disabilities that it causes and its association with various microvascular complications, most importantly retinopathy. A 24-year-old male patient, with type 1 diabetes of 20 years duration, presented to us with difficulties in performing fine motor tasks such as buttoning his shirt and with positive “Namaste” sign and “Table Top” sign. He had reduced sensation on monofilament testing, decreased vibration perception threshold, and a nerve conduction study suggested distal sensory demyelinating and axonal polyneuropathy. He had a restrictive pattern on pulmonary function tests, normal lung parenchyma on high-resolution computed tomography of his thorax, proliferative diabetic retinopathy, proteinuria, vitamin D deficiency, and subclinical hypothyroidism. He was followed closely with tight glycemic control and physiotherapy. In rural setups, DCA can act as a mirror to screen for macrovascular and microvascular complications if not already done routinely or previously. Management includes physiotherapy, glycemic control, patient education, and regular follow-up, with surgical procedures being only the last option.
Revisiting the lineage contribution of hematopoietic stem and progenitor cells
Authors: Gao Suwei , Zhang Yifan , Liu Feng 
Published: July 2023

ABSTRACT
For a long time, self-renewing and multipotent hematopoietic stem cells (HSCs) have been thought to make a major contribution to both embryonic and adult hematopoiesis. The canonical hematopoietic hierarchy illustrating HSC self-renewal and multipotency has been established mainly based on invasive functional assays (e.g. transplantation or colony-forming units in the spleen and in culture), which evaluate the cellular potentials of HSCs. With the extensive applications of non-invasive cell fate-mapping strategies, recent lineage tracing-based studies have suggested that not all native hematopoiesis is established via the hierarchical differentiation of HSCs. By contrast, hematopoietic progenitor cells (HPCs) are a dominant contributor to both embryonic and young adult hematopoiesis. These new findings help redefine the cellular origins of embryonic and adult hematopoiesis under native conditions, and emphasize the differences in revealing HSC potential versus HSC fate using distinct approaches during stress and native hematopoiesis. Here, we review recent advances in HPC and HSC development, and provide an updated perspective to incorporate these new findings with our traditional understanding of developmental and adult hematopoiesis.
UMAD1 contributes to ESCRT-III dynamic subunit turnover during cytokinetic abscission
Authors: Glover James , Scourfield Edward J. , Ventimiglia Leandro N. , Yang Xiaoping , Lynham Steven , Agromayor Monica , Martin-Serrano Juan 
Published: July 2023

ABSTRACT
Abscission is the final stage of cytokinesis whereby the midbody, a thin intercellular bridge, is resolved to separate the daughter cells. Cytokinetic abscission is mediated by the endosomal sorting complex required for transport (ESCRT), a conserved membrane remodelling machinery. The midbody organiser CEP55 recruits early acting ESCRT factors such as ESCRT-I and ALIX (also known as PDCD6IP), which subsequently initiate the formation of ESCRT-III polymers that sever the midbody. We now identify UMAD1 as an ESCRT-I subunit that facilitates abscission. UMAD1 selectively associates with VPS37C and VPS37B, supporting the formation of cytokinesis-specific ESCRT-I assemblies. TSG101 recruits UMAD1 to the site of midbody abscission, to stabilise the CEP55–ESCRT-I interaction. We further demonstrate that the UMAD1–ESCRT-I interaction facilitates the final step of cytokinesis. Paradoxically, UMAD1 and ALIX co-depletion has synergistic effects on abscission, whereas ESCRT-III recruitment to the midbody is not inhibited. Importantly, we find that both UMAD1 and ALIX are required for the dynamic exchange of ESCRT-III subunits at the midbody. Therefore, UMAD1 reveals a key functional connection between ESCRT-I and ESCRT-III that is required for cytokinesis.
Comparison of clinical effects between microscopic surgery and conventional surgery in children with penile hypospadias and difference analysis of postoperative urodynamics
Authors: Guo Shi-lei , Zheng Wei , Shi Xiao-qing , Zhang Bo-song , Wang Jie 
Published: July 2023

Objective: To compare and analyze the clinical effects of microscopic surgery and conventional surgery in children with penile hypospadias and the differences in postoperative urodynamic indexes.
Methods: It was a clinical comparative study. A total of 80 children with penile hypospadias admitted to Beijing Children’s Hospital Affiliated to Capital Medical University Baoding Hospital from July 2018 to September 2022 were selected and randomly divided into two group. The experimental group were treated with microscopic urethroplasty, while the control group were treated with traditional urethroplasty. The operative effect, operation time, total intraoperative blood loss, postoperative hospital stay and incidence of surgical complications were compared and analyzed between the two groups. All the children were followed up for two years, and the changes in urodynamic parameters including maximum urine flow rate (Qmax), average urine flow rate (Qavc), urine flow time (FT), peak time (TQmax) and residual urine (PVR) were compared before, two weeks after, six months after and two years after surgery.
Results: The efficacy of the experimental group was significantly higher than that of the control group (p=0.013). The intraoperative blood loss and postoperative hospital stay in the experimental group were significantly better than those in the control group (p=0.000). The incidences of urinary leakage and urethral stricture in the experimental group were lower than those in the control group (p<0.05). The Qmax level in the experimental group was higher than that in the control group at six months and two years after surgery, while the FT level was lower than that of the control group (p<0.05).
Conclusion: Microscopic surgery is a method with significant clinical value in the treatment of penile hypospadias.
doi: https://doi.org/10.12669/pjms.39.5.6986
How to cite this: Guo S, Zheng W, Shi X, Zhang B, Wang J. Comparison of clinical effects between microscopic surgery and conventional surgery in children with penile hypospadias and difference analysis of postoperative urodynamics. Pak J Med Sci. 2023;39(5):---------. doi: https://doi.org/10.12669/pjms.39.5.6986
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Diagnostic utility of mast cell analysis in hypoplastic bone marrows for differentiation of aplastic anaemia from hypoplastic myelodysplastic neoplasm: A retrospective study
Authors: G V Chaithra , Gupta Soumya , Rao Ranjitha , Rai Sharada , Murali Nirupama , Hegde Sunita 
Published: July 2023

Background: Haematological disorders characterized by hypocellular marrow like aplastic anaemia (AA) and hypocellular myelodysplastic neoplasm (MDS-h) are diagnostic challenges as the clinical and morphological features overlap, while the treatment and prognosis differ. Bone marrow mast cell quantification is proposed as a supplementary diagnostic and prognostic tool to differentiate AA from MDS-h. We aim to study the distribution of mast cells in hypoplastic marrow and determine its role in differential diagnosis of AA and MDS-h. Methods: We analysed bone marrow biopsies of 65 cases of hypoplastic/aplastic marrow received during the year 2015-2021 for the distribution of mast cells using Toluidine Blue special staining. Hematopoietic stem cells were assessed with the help of CD34 immunohistochemistry. Results: Increased mast cells were noted in 55.4% of all the cases, of which 48% were cases of AA and 21% were cases of MDS-h (P: 0.04). Overall, 76% of AA and 33% of MDS-h cases showed increased numbers of mast cells. Reduced hematopoietic stem cells were noted in 69.4% of the cases with elevated mast cells (P: 0.1). Conclusions: Mast cell quantification in trephine biopsy of AA and MDS-h can act as a supplementary diagnostic tool and guide the management of the respective entities. Understanding its role in the bone marrow niche can enhance stem cell transplant treatment.
A comparative evaluation of different scores in predicting severity and outcome in acute pancreatitis
Authors: Mahajan Ojas , Mahajan Satish , Acharya Sourya , Wanjari Anil , Kumar Sunil , Bawankule Shilpa , Giri Anamika , Khurana Kashish 
Published: July 2023

Background: Acute pancreatitis (AP) is an inflammatory condition usually caused by alcohol or gallstones. Our goal was to prospectively compare the diagnostic efficacy of the Acute Physiology & Chronic Health Evaluation (APACHE) II, the Bedside Index of Severity in Acute Pancreatitis (BISAP), the Ranson's score & the Modified Glasgow Score (MGS) in determining the severity & outcome of Acute pancreatitis in a tertiary care facility in central India. Methods: Between December 2020 & December 2022, this prospective observational study was done in rural area of Wardha district. 110 subjects were included, and the diagnosis of acute pancreatitis was done using Atlanta criteria. APACHE II, MGS, Ranson score on admission, Ranson score 48 hours after admission & BISAP were used to evaluate each subject. The reciever operating curve was used to measure the specificity, sensitivity, NPV, PPV, diagnostic accuracy, area under the curve (AUC) & these scoring methods were then prospectively compared. Results: When a cut-off based on the literature was used, the APACHE II score could accurately diagnose severe cases of AP (n=110) in 69 patients, BISAP in 68 patients, MGS in 49, Ranson score on admission in 48 patients & after 48 hours in 48 patients. This study showed that Ranson score 48 hours after admission had a AUC (0.991), Ranson score at admission (AUC 0.989) & Modified Glasgow Scale (AUC 0.6486) had fair accuracy as compared to APACHE II (AUC 0.974) & BISAP (AUC 0.896) for determining the level of severity among AP patients based on ROC curves. Conclusion: To predict the severity of AP, the Ranson score after 48 hours showed the highest NPV, PPV, sensitivity, specificity, and diagnostic accuracy of all the scoring methods tested. The BISAP score had the highest specificity, sensitivity, PPV& NPV for determining the outcome of AP.
Factors associated with knowledge and use of home pregnancy test kits in Uganda
Authors: Kamei Akito , Sato Ryoko , Thornton Rebecca 
Published: July 2023

Early detection of pregnancy status may help women initiate earlier antenatal care and healthy pregnancy behaviors, which could lead to healthier mothers and infants. Pregnancy tests are inexpensive and easy to use; meanwhile, little attention has been given to understanding women’s knowledge and use of home pregnancy tests, especially in developing countries. We analyze cross-sectional data collected from 1,008 women ages 18–35, living in Northern Uganda in 2019, who are most likely to be uncertain about their pregnancy status. The survey asked women if they had knowledge of or had ever used a home pregnancy test kit, and barriers to purchasing a home pregnancy test kit. Among the 1,008 women, 65 percent report knowledge of home pregnancy test kits, and 29 percent report having ever used a test kit. Women who have heard of pregnancy test kits have higher levels of education, are in higher wealth quintiles, are more likely to have a salaried occupation and live closer to a health facility. Among women who report knowledge of home pregnancy test kits (N = 657), 90 percent report needing to ask their husband or partner for money to purchase a test kit, seven percent report they would hide the purchase, and 31 percent report that their husband or partner would not support the purchase. Women who report a lack of support from their husband or partner tend to be older, are more likely to have had prior pregnancies, are less likely to have a salaried occupation, are less likely to want a/another child, and are more likely to have a husband or partner desiring more children than herself. Future research aimed at understanding how and whether these barriers affect the utilization of home pregnancy test kits could help inform policymakers on how to increase the use of home pregnancy test kits.
Trial registration: NCT03975933. Registered 05 June 2019, https://clinicaltrials.gov/ct2/show/record/NCT03975933.
Characterization of Latin American migrants at risk for Trypanosoma cruzi infection in a non-endemic setting. Insights into initial evaluation of cardiac and digestive involvement
Authors: Laynez-Roldán Pedro , Losada-Galván Irene , Posada Elizabeth , de la Torre Ávila Leonardo , Casellas Aina , Sanz Sergi , Subirà Carme , Rodriguez-Valero Natalia , Camprubí-Ferrer Daniel , Vera Isabel , Roldán Montserrat , Aldasoro Edelweiss , Oliveira-Souto Inés , Calvo-Cano Antonia , Valls Maria-Eugenia , Álvarez-Martínez Míriam J. , Gállego Montserrat , Abras Alba , Ballart Cristina , Muñoz José , Gascón Joaquim , Pinazo Maria-Jesus 
Published: July 2023

Background
Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries.

Methods
The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram.

Results
Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram.

Conclusions
We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal.
A systematic review on maternal-to-infant transfer of drugs through breast milk during the treatment of malaria, tuberculosis, and neglected tropical diseases
Authors: Ojara Francis Williams , Kawuma Aida N. , Waitt Catriona 
Published: July 2023

BackgroundExclusive breastfeeding of infants under 6 months of age is recommended by the World Health Organization. In 2021, over 300 million combined incident cases of malaria, tuberculosis, and neglected tropical diseases (NTDs) were reported, predominantly in low-income countries. For many of the drugs used as first-line treatments for these conditions, there is limited knowledge on infant exposure through breastfeeding with poorly understood consequences. This review summarized available knowledge on mother-to-infant transfer of these drugs to inform future lactation pharmacokinetic studies.MethodologyA list of first-line drugs was generated from the latest WHO treatment guidelines. Using standard online databases, 2 independent reviewers searched for eligible articles reporting lactation pharmacokinetics studies and extracted information on study design, participant characteristics, and the mathematical approach used for parameter estimation. A third reviewer settled any disagreements between the 2 reviewers. All studies were scored against the standardized “ClinPK” checklist for conformity to best practices for reporting clinical pharmacokinetic studies. Simple proportions were used to summarize different study characteristics.FindingsThe most remarkable finding was the scarcity of lactation pharmacokinetic data. Only 15 of the 69 drugs we listed had lactation pharmacokinetics fully characterized. Most studies enrolled few mothers, and only one evaluated infant drug concentrations. Up to 66% of the studies used non-compartmental analysis to estimate pharmacokinetic parameters rather than model-based compartmental analysis. Unlike non-compartmental approaches, model-based compartmental analysis provides for dynamic characterization of individual plasma and breast milk concentration-time profiles and adequately characterizes variability within and between individuals, using sparsely sampled data. The “ClinPK” checklist inadequately appraised the studies with variability in the number of relevant criteria across different studies.Conclusions/significanceA consensus is required on best practices for conducting and reporting lactation pharmacokinetic studies, especially in neglected diseases such as malaria, tuberculosis, and NTDs, to optimize treatment of mother–infant pairs.
Snakebite envenomations and access to treatment in communities of two indigenous areas of the Western Brazilian Amazon: A cross-sectional study
Authors: de Farias Altair Seabra , Gomes Filho Manoel Rodrigues , da Costa Arévalo Macio , Cristino Joseir Saturnino , Farias Franciane Ribeiro , Sachett André , Silva-Neto Alexandre Vilhena , de Carvalho Fabíola Guimarães , Ambrosio Sediel Andrade , da Silva Carvalho Erica , Lacerda Marcus , Murta Felipe , Machado Vinícius Azevedo , Wen Fan Hui , Monteiro Wuelton , Sachett Jacqueline 
Published: July 2023

Background
The indigenous populations of Brazil present poor health indicators and a disproportionate prevalence and case-fatality rate of neglected tropical diseases, including snakebite envenomations (SBEs). This study aims to estimate access to medical care for SBEs and analyze the barriers that prevent victims from accessing healthcare in indigenous communities in two health districts located in the Western Brazilian Amazon.

Methodology/Principal findings
This cross-sectional study used semi-structured interviews to collect data from individuals who experienced SBEs in the Upper Rio Solimões and Upper Rio Negro indigenous health districts. Of the 187 participants, 164 (87.7%) reported that they had access to healthcare and received assistance in a hospital in the urban area of the municipalities. Frequency was 95.4% in the Upper Rio Solimões SIHD, and 69.6% in the Upper Rio Negro SIHD (P<0.0001). The study found that the availability of indigenous medicine as the only choice in the village was the main reason for not accessing healthcare (75%), followed by a lack of financial resources and means of transportation (28.1%). Four deaths were reported from SBEs, resulting in a case-fatality rate of 2.1%.

Conclusions/Significance
In the study areas, there are records of SBE patients who did not receive medical attention. Availability of pre-hospital emergency transport using motorboats, a greater number of hospitals and better navigability of the Solimões River and its tributaries would make access easier for indigenous people living in the region of the Upper Solimões River. The implementation of cross-cultural hospital care needs to be considered in order to reduce the resistance of indigenous populations in relation to seeking treatment for SBEs.