bluuebunny/crossref_metadata_2025_split huggingface dataset:
T-replete HLA-matched grafts vs T-depleted HLA-mismatched grafts in inborn errors of immunity
Authors: Lum Su Han , Greener Sinéad , Perez-Heras Inigo , Drozdov Daniel , Payne Rebecca P. , Watson Helen , Carruthers Kay , January Robert , Nademi Zohreh , Owens Stephen , Williams Eleri , Waugh Sheila , Burton-Fanning Shirelle , Leahy Timmothy Ronan , Cant Andrew , Abinun Mario , Flood Terry , Hambleton Sophie , Gennery Andrew R. , Slatter Mary 
Published: December 2021

Abstract
Hematopoietic cell transplantation (HCT) has become standard-of-care for an increasing number of inborn errors of immunity (IEI). This report is the first to compare transplant outcomes according to T-cell–replete (ie, T-replete) HLA-matched grafts using alemtuzumab (n = 117) and T-cell–depleted (ie, T-depleted) HLA-mismatched grafts using T-cell receptor-αβ (TCRαβ)/CD19 depletion (n = 47) in children with IEI who underwent first HCT between 2014 and 2019. All patients received treosulfan-based conditioning except patients with DNA repair disorders. For T-replete grafts, the stem cell source was marrow in 25 (21%) patients, peripheral blood stem cell (PBSC) in 85 (73%), and cord blood in 7 (6%). TCRαβ/CD19 depletion was performed on PBSCs from 45 haploidentical parental donors and 2 mismatched unrelated donors. The 3-year overall survival (OS) and event-free survival for the entire cohort were 85% (77%-90%) and 79% (69%-86%), respectively. Analysis according to age at transplant revealed a comparable 3-year OS between T-replete grafts (88%; 76%-94%) and T-depleted grafts (87%; 64%-96%) in younger patients (aged &lt;5 years at HCT). For older patients (aged &gt;5 years), the OS was significantly lower in T-depleted grafts (55%; 23%-78%) compared with T-replete grafts (87%; 68%-95%) (P = .03). Grade III to IV acute graft-versus-host disease was observed in 8% of T-replete marrow, 7% of T-replete PBSC, 14% of T-replete cord blood, and 2% of T-depleted PBSC (P = .73). Higher incidence of viremia (P &lt; .001) and delayed CD3 reconstitution (P = .003) were observed after T-depleted graft HCT. These data indicate that mismatched donor transplant after TCRαβ/CD19 depletion represents an excellent alternative for younger children with IEI in need of an allograft.
Extent of intravital contraction of arterial and venous thrombi and pulmonary emboli
Authors: Khismatullin Rafael R. , Abdullayeva Shahnoza , Peshkova Alina D. , Sounbuli Khetam , Evtugina Natalia G. , Litvinov Rustem I. , Weisel John W. 
Published: December 2021

Abstract
Blood clots and thrombi undergo platelet-driven contraction/retraction followed by structural rearrangements. We have established quantitative relationships between the composition of blood clots and extent of contraction to determine intravital contraction of thrombi and emboli based on their content. The composition of human blood clots and thrombi was quantified using histology and scanning electron microscopy. Contracting blood clots were segregated into the gradually shrinking outer layer that contains a fibrin-platelet mesh and the expanding inner portion with compacted red blood cells (RBCs). At 10% contraction, biconcave RBCs were partially compressed into polyhedral RBCs, which became dominant at 20% contraction and higher. The polyhedral/biconcave RBC ratio and the extent of contraction displayed an exponential relationship, which was used to determine the extent of intravital contraction of ex vivo thrombi, ranging from 30% to 50%. In venous thrombi, the extent of contraction decreased gradually from the older (head) to the younger (body, tail) parts. In pulmonary emboli, the extent of contraction was significantly lower than in the venous head but was similar to the body and tail, suggesting that the emboli originate from the younger portion(s) of venous thrombi. The extent of contraction in arterial cerebral thrombi was significantly higher than in the younger parts of venous thrombi (body, tail) and pulmonary emboli but was indistinguishable from the older part (head). A novel tool, named the “contraction ruler,” has been developed to use the composition of ex vivo thrombi to assess the extent of their intravital contraction, which contributes to the pathophysiology of thromboembolism.
Post–hematopoietic stem cell transplantation immune-mediated anemia: a literature review and novel therapeutics
Authors: Migdady Yazan , Pang Yifan , Kalsi Shelley S. , Childs Richard , Arai Sally 
Published: December 2021

AbstractAnemia after allogeneic hematopoietic stem cell transplantation (HSCT) can be immune or non–immune mediated. Auto- or alloimmunity resulting from blood group incompatibility remains an important cause in post-HSCT immune-mediated anemia. ABO incompatibility is commonly encountered in HSCT and may lead to serious clinical complications, including acute hemolysis, pure red cell aplasia, and passenger lymphocyte syndrome. It remains controversial whether ABO incompatibility may affect HSCT outcomes, such as relapse, nonrelapse mortality, graft-versus-host disease, and survival. Non-ABO incompatibility is less frequently encountered but can have similar complications to ABO incompatibility, causing adverse clinical outcomes. It is crucial to identify the driving etiology of post-HSCT anemia in order to prevent and treat this condition. This requires a comprehensive understanding of the mechanism of anemia in blood group–incompatible HSCT and the temporal association between HSCT and anemia. In this review, we summarize the literature on post-HSCT immune-mediated anemia with a focus on ABO and non-ABO blood group incompatibility, describe the underlying mechanism of anemia, and outline preventive and treatment approaches.
Does disrespect and abuse during childbirth differ between public and private hospitals in Southeast Nigeria
Authors: Okedo-Alex Ijeoma Nkem , Akamike Ifeyinwa Chizoba , Eze Irene Ifeyinwa , Onwasigwe Chika Nwamma 
Published: December 2021

Abstract
Background
Disrespect and Abuse (D&A) during childbirth represents an important barrier to skilled birth utilization, indicating a problem with quality of care and a violation of women‘s human rights. This study compared prevalence of D&A during childbirth in a public and a private hospital in Southeast Nigeria.

Methods
This study was a cross-sectional study among women who gave birth in two specialized health facilities: a public teaching and a private-for-profit faith-based hospital in Southeast Nigeria. In each facility, systematic random sampling was used to select 310 mothers who had given birth in the facility and were between 0-14 weeks after birth. Study participants were recruited through the immunization clinics. Semi-structured, interviewer-administered questionnaires using the Bowser and Hills classification of D&A during childbirth were used for data collection. Data were analyzed using SPSS version 20 at 95% significance level.

Results
Mean age of the participants in the public hospital was 30.41 ± 4.4 and 29.31 ± 4.4 in the private hospital. Over three-fifths (191; 61.6%) in the public and 156 women (50.3%) in the private hospital had experienced at least one form of D&A during childbirth [cOR1.58; 95% CI 1.15, 2.18]. Abandonment and neglect [Public153 (49.4%) vs. Private: 91 (29.4%); cOR2.35; 95% CI. 1.69, 3.26] and non-consented care [Public 45 (14.5%) vs. Private 67(21.6%): cOR0.62; 95% CI. 0.41, 0.93] were the major types of D&A during childbirth. Denial of companionship was the most reported subtype of D&A during childbirth in both facilities [Public 135 (43.5%) vs. Private66 (21.3%); cOR2.85; 95% CI. 2.00, 4.06]. Rural residents were less likely to report at least one form of D&A during childbirth (aOR 0.53; CI 0.35-0.79).

Conclusion
Although prevalence was high in both facilities, overall prevalence of D&A during childbirth and most subtypes were higher in the public health facility. There is a need to identify contextual factors enabling D&A during childbirth in public and private health care settings.
Pregnant during the COVID-19 pandemic: an exploration of patients’ lived experiences
Authors: Kolker Sabrina , Biringer Anne , Bytautas Jessica , Blumenfeld Haley , Kukan Sahana , Carroll June C. 
Published: December 2021

Abstract
Background
Infectious outbreaks are known to cause fear and panic. Exploration of pregnant individuals’ psychosocial condition using a qualitative lens during an infectious outbreak is limited. In this study we explore pregnant individuals’ lived experiences as well as their psychological and behavioural responses during COVID-19 with the goal of providing useful strategies from the patient’s perspective to enable health care providers to help pregnant patients navigate this and future pandemics.

Methods
Pregnant individuals between 20-weeks gestation and 3 months postpartum who received maternity care from an urban academic interprofessional teaching unit in Toronto, Canada were invited to participate. Semi-structured 60 min interviews were audio-recorded, transcribed and analyzed using descriptive thematic analysis. Interview questions probed psychological responses to the pandemic, behavioural and lifestyle changes, strategies to mitigate distress while pregnant during COVID-19 and advice for other patients and the healthcare team.

Results
There were 12 participants, mean age 35 years (range 30–43 years), all 1 to 6 months postpartum. Six main themes emerged: 1) Childbearing-related challenges to everyday life; 2) Increased worry, uncertainty and fear; 3) Pervasive sense of loss; 4) Challenges accessing care; 5) Strategies for coping with pandemic stress; 6) Reflections and advice to other pregnant people and health care professionals. Pregnant individuals described lack of social support due to COVID-19 pandemic restrictions and a profound sense of loss of what they thought their pregnancy and postpartum period should have been. Advice to healthcare providers included providing mental health support, clear and up to date communication as well as more postpartum and breastfeeding support.

Conclusions
These participants described experiencing psychosocial distress during their pregnancies and postpartum. In a stressful situation such as a global pandemic, health care providers need to play a pivotal role to ensure pregnant individuals feel supported and receive consistent care throughout the pregnancy and postpartum period. The health care provider should ensure that mental health concerns are addressed and provide postpartum and breastfeeding support. Without addressing this need for support, parental mental health, relationships, parent-infant bonding, and infant development may be negatively impacted.
Factors associated with mammographic breast density among women in Karachi Pakistan
Authors: Shamsi Uzma , Afzal Shaista , Shamsi Azra , Azam Iqbal , Callen David 
Published: December 2021

Abstract
Background
There are no studies done to evaluate the distribution of mammographic breast density and factors associated with it among Pakistani women.

Methods
Participants included 477 women, who had received either diagnostic or screening mammography at two hospitals in Karachi Pakistan. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System. In person interviews were conducted using a detailed questionnaire, to assess risk factors of interest, and venous blood was collected to measure serum vitamin D level at the end of the interview. To determine the association of potential factors with mammographic breast density, multivariable polytomous logistic regression was used.

Results
High-density mammographic breast density (heterogeneously and dense categories) was high and found in 62.4% of women. There was a significant association of both heterogeneously dense and dense breasts with women of a younger age group < 45 years (OR 2.68, 95% CI 1.60–4.49) and (OR 4.83, 95% CI 2.54–9.16) respectively. Women with heterogeneously dense and dense breasts versus fatty and fibroglandular breasts had a higher history of benign breast disease (OR 1.90, 95% CI 1.14–3.17) and (OR 3.61, 95% CI 1.90–6.86) respectively. There was an inverse relationship between breast density and body mass index. Women with dense breasts and heterogeneously dense breasts had lower body mass index (OR 0.94 95% CI 0.90–0.99) and (OR 0.81, 95% CI 0.76–0.87) respectively. There was no association of mammographic breast density with serum vitamin D levels, diet, and breast cancer.

Conclusions
The findings of a positive association of higher mammographic density with younger age and benign breast disease and a negative association between body mass index and breast density are important findings that need to be considered in developing screening guidelines for the Pakistani population.
Cost-Effectiveness of perioperative Vaginally Administered estrogen in postmenopausal women undergoing prolapse surgery (EVA trial): study protocol for a multicenter double-blind randomized placebo-controlled trial
Authors: Vodegel Eva V. , Zwolsman Sandra E. , Vollebregt Astrid , Duijnhoven Ruben G. , Bosmans Judith E. , Speksnijder Leonie , Roos Eveline J. , Spaans Wilbert , Gerards Franca , Adriaanse Albert , Vernooij Flora , Milani Alfredo L. , Sikkema Marko , Weemhoff Mirjam , Mous Marieke , Damoiseaux Anne , van Dongen Heleen , v/d Ploeg Marinus , Veen Joggem , van de Pol Geerte , Broekman Bart , Steures Pieternel , Tjin-Asjoe Fernando , van der Stege Jolande , Mouw Ronald , van der Vaart Carl H. , Roovers Jan-Paul W. R. 
Published: December 2021

Abstract
Background
Surgery for pelvic organ prolapse (POP) is associated with high recurrence rates. The costs associated with the treatment of recurrent POP are huge, and the burden from women who encounter recurrent POP, negatively impacts their quality of life. Estrogen therapy might improve surgical outcome for POP due to its potential beneficial effects. It is thought that vaginal estrogen therapy improves healing and long-term maintenance of connective tissue integrity. Hence, this study aims to evaluate the cost-effectiveness of perioperative vaginal estrogen therapy in postmenopausal women undergoing POP surgery.

Methods
The EVA trial is a multi-center double-blind randomized placebo-controlled trial conducted in the Netherlands comparing the effectiveness and costs-effectiveness of vaginal estrogen therapy. This will be studied in 300 postmenopausal women undergoing primary POP surgery, with a POP-Q stage of ≥ 2. After randomization, participants administer vaginal estrogen cream or placebo cream from 4 to 6 weeks preoperative until 12 months postoperative. The primary outcome is subjective improvement of POP symptoms at 1 year follow-up, measured with the Patient Global Impression of Improvement (PGI-I) scale. Secondary outcomes are POP-Q anatomy in all compartments, re-interventions, surgery related complications, general and disease specific quality of life, sexual function, signs and complaints of vaginal atrophy, vaginal pH, adverse events, costs, and adherence to treatment. Follow up is scheduled at 6 weeks, 6 months and 12 months postoperative. Data will be collected using validated questionnaires and out-patient visits including gynecological examination performed by an independent gynecologist.

Discussion
This study investigates whether perioperative vaginal estrogen will be cost-effective in the surgical treatment of POP in postmenopausal women. It is hypothesized that estrogen therapy will show a reduction in recurrent POP symptoms and a reduction in reoperations for POP, with subsequent improved quality of life among women and cost savings.

Trial registrationNetherlands Trial Registry: NL6853; registered 19-02-2018, https://www.trialregister.nl/trial/6853. EudraCT: 2017-003144-21; registered: 24-07-2017.
An in vivo evaluation of anti-inflammatory, analgesic and anti-pyretic activities of newly synthesized 1, 2, 4 Triazole derivatives
Authors: Azim Tabinda , Wasim Muhammad , Akhtar Muhammad Shoaib , Akram Irfan 
Published: December 2021

AbstractBackgroundIn recent years, 1, 2, 4-triazole and its derivatives have been reported to be pharmacologically significant scaffolds. They possess analgesic, anti-tubercular, anti-inflammatory, anti-convulsant, anti-oxidant, anti-fungal, anti-cancer, anxiolytic and anti-depressant activity. This study was designed and conducted to evaluate the potential anti-inflammatory, analgesic and antipyretic activities of Triazole derivatives.MethodsSwiss albino (male and female) mice weighing 20-30 g (10-24 weeks female), (5-14 weeks male) and Wister Kyoto rats (male and female) weighing 200-300 g (8-10 weeks old) were used for the present study. Anti-inflammatory activity was checked using Lambda carrageenan (λ) and egg albumin-induced paw edema models. Analgesic via Writhing Reflex induced by acetic acid and formalin, furthermore anti-pyretic activity was assessed by yeast induced pyrexia.ResultsBoth of the test compounds exhibited encouraging anti-inflammatory analgesic and antipyretic results when compared with standard drug ibuprofen. The maximum inhibition of edema for the compound (S)-1-(4-Amino-5-mercapto-4H-1,2,4-triazole-3-yl) ethanol[3]was found to be (91)% as compared to reference drug ibuprofen (82)%, while (S)-1-(6-Phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)ethanol[5e]showed equipotent results to ibuprofen (81)%. The derivatives were also screened for their anti-nociceptive activity by Acetic acid writhing and tail immersion test. Compound 3 showed a significant reduction in wriths (83)% as compared to standard drug ibuprofen 71.5% and [5] showed comparable results to ibuprofen by exhibiting 70% reduction in writh at the same dose as that of standard drug, moreover, there were no signs of toxicity being observed after administration of high doses of test compounds to mice.ConclusionsIt is evident from the results that compounds 3(compound A) and 5(compound B) are a potential candidate for anti-inflammatory, analgesic and anti-pyretic and the scaffold could be used for further structural modifications. Further studies would help to evaluate their molecular mechanism of action regarding these beneficial activities.
Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy
Authors: Ou Weijun , Yang Joshua , Simanauskaite Juste , Choi Matthew , Castellanos Demi M. , Chang Rudy , Sun Jiahong , Jagadeesan Nataraj , Parfitt Karen D. , Cribbs David H. , Sumbria Rachita K. 
Published: December 2021

Abstract
Background
Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via receptor-mediated transcytosis. The present study aimed to investigate the effects of TfRMAb-TNFR (BBB-penetrating TNFI) and etanercept (non-BBB-penetrating TNFI) in the PS19 transgenic mouse model of tauopathy.

Methods
Six-month-old male and female PS19 mice were injected intraperitoneally with saline (n = 12), TfRMAb-TNFR (1.75 mg/kg, n = 10) or etanercept (0.875 mg/kg, equimolar dose of TNFR, n = 10) 3 days/week for 8 weeks. Age-matched littermate wild-type mice served as additional controls. Blood was collected at baseline and 8 weeks for a complete blood count. Locomotion hyperactivity was assessed by the open-field paradigm. Brains were examined for phosphorylated tau lesions (Ser202, Thr205), microgliosis, and neuronal health. The plasma pharmacokinetics were evaluated following a single intraperitoneal injection of 0.875 mg/kg etanercept or 1.75 mg/kg TfRMAb-TNFR or 1.75 mg/kg chronic TfRMAb-TNFR dosing for 4 weeks.

Results
Etanercept significantly reduced phosphorylated tau and microgliosis in the PS19 mouse brains of both sexes, while TfRMAb-TNFR significantly reduced these parameters in the female PS19 mice. Both TfRMAb-TNFR and etanercept treatment improved neuronal health by significantly increasing PSD95 expression and attenuating hippocampal neuron loss in the PS19 mice. The locomotion hyperactivity in the male PS19 mice was suppressed by chronic etanercept treatment. Equimolar dosing resulted in eightfold lower plasma exposure of the TfRMAb-TNFR compared with etanercept. The hematological profiles remained largely stable following chronic biologic TNFI dosing except for a significant increase in platelets with etanercept.

Conclusion
Both TfRMAb-TNFR (BBB-penetrating) and non-BBB-penetrating (etanercept) biologic TNFIs showed therapeutic effects in the PS19 mouse model of tauopathy.
An optimized FM-index library for nucleotide and amino acid search
Authors: Anderson Tim , Wheeler Travis J. 
Published: December 2021

Abstract
Background
Pattern matching is a key step in a variety of biological sequence analysis pipelines. The FM-index is a compressed data structure for pattern matching, with search run time that is independent of the length of the database text. Implementation of the FM-index is reasonably complicated, so that increased adoption will be aided by the availability of a fast and flexible FM-index library.

Results
We present AvxWindowedFMindex (AWFM-index), a lightweight, open-source, thread-parallel FM-index library written in C that is optimized for indexing nucleotide and amino acid sequences. AWFM-index introduces a new approach to storing FM-index data in a strided bit-vector format that enables extremely efficient computation of the FM-index occurrence function via AVX2 bitwise instructions, and combines this with optional on-disk storage of the index’s suffix array and a cache-efficient lookup table for partial k-mer searches. The AWFM-index performs exact match count and locate queries faster than SeqAn3’s FM-index implementation across a range of comparable memory footprints. When optimized for speed, AWFM-index is $$\sim $$
∼
2–4x faster than SeqAn3 for nucleotide search, and $$\sim $$
∼
2–6x faster for amino acid search; it is also $$\sim $$
∼
4x faster with similar memory footprint when storing the suffix array in on-disk SSD storage.

Conclusions
AWFM-index is easy to incorporate into bioinformatics software, offers run-time performance parameterization, and provides clients with FM-index functionality at both a high-level (count or locate all instances of a query string) and low-level (step-wise control of the FM-index backward-search process). The open-source library is available for download at https://github.com/TravisWheelerLab/AvxWindowFmIndex.