bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gata2 haploinsufficiency promotes proliferation and functional decline of hematopoietic stem cells with myeloid bias during aging
Authors: Abdelfattah Ali , Hughes-Davies Antonia , Clayfield Liam , Menendez-Gonzalez Juan Bautista , Almotiri Alhomidi , Alotaibi Badi , Tonks Alex , Rodrigues Neil P. 
Published: September 2021

Abstract
During aging, hematopoietic stem cell (HSC) function wanes with important biological and clinical implications for benign and malignant hematology, and other comorbidities, such as cardiovascular disease. However, the molecular mechanisms regulating HSC aging remain incompletely defined. GATA2 haploinsufficiency driven clinical syndromes initially result in primary immunodeficiencies and routinely evolve into hematologic malignancies on acquisition of further epigenetic mutations in both young and older patients. Using a conditional mouse model of Gata2 haploinsufficiency, we discover that during aging Gata2 promotes HSC proliferation, monocytosis, and loss of the common lymphoid progenitor. Aging of Gata2 haploinsufficient mice also offsets enhanced HSC apoptosis and decreased granulocyte-macrophage progenitor number normally observed in young Gata2 haploinsufficient mice. Transplantation of elderly Gata2 haploinsufficient HSCs impairs HSC function with evidence of myeloid bias. Our data demonstrate that Gata2 regulates HSC aging and suggest the mechanisms by which Gata2 mediated HSC aging has an impact on the evolution of malignancies in GATA2 haploinsufficiency syndromes.
Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma–type Richter syndrome
Authors: Herrera Alex F. , Ahn Kwang Woo , Litovich Carlos , Chen Yue , Assal Amer , Bashir Qaiser , Bayer Ruthee-Lu , Coleman Melanie , DeFilipp Zachariah , Farhadfar Nosha , Greenwood Matthew , Hahn Theresa , Horwitz Mitchell , Jacobson Caron , Jaglowski Samantha , Lachance Sylvie , Langston Amelia , Mattar Bassam , Maziarz Richard T. , McGuirk Joseph , Mian Mohammad A. H. , Nathan Sunita , Phillips Adrienne , Rakszawski Kevin , Sengeloev Henrik , Shenoy Shalini , Stuart Robert , Sauter Craig S. , Kharfan-Dabaja Mohamed A. , Hamadani Mehdi 
Published: September 2021

Abstract
Richter syndrome (RS) represents a transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), which is associated with a dismal prognosis. Patients with DLBCL-RS have poor outcomes with DLBCL-directed therapy; thus, consolidation with hematopoietic cell transplantation (HCT) has been used, with durable remissions observed. Studies reporting HCT outcomes in patients with DLBCL-RS have been small, have not evaluated the prognostic impact of cytogenetic risk factors, and were conducted prior to the era of novel targeted therapy of CLL/SLL. We performed a Center for International Blood and Transplant Research registry study evaluating outcomes after autologous HCT (auto-HCT; n = 53) and allogeneic HCT (allo-HCT; n = 118) in patients with DLBCL-RS treated in the modern era. More auto-HCT recipients were in complete response (CR) at HCT relative to allo-HCT recipients (66% vs 34%), whereas a higher proportion of allo-HCT recipients had 17p deletion (33% vs 7%) and had previously received novel agents (39% vs 10%). In the auto-HCT cohort, the 3-year relapse incidence, progression-free survival (PFS), and overall survival (OS) were 37%, 48%, and 57%, respectively. Among allo-HCT recipients, the 3-year relapse incidence, PFS, and OS were 30%, 43%, and 52%, respectively. In the allo-HCT cohort, deeper response at HCT was associated with outcomes (3-year PFS/OS, 66%/77% CR vs 43%/57% partial response vs 5%/15% resistant; P &lt; .0001 for both), whereas cytogenetic abnormalities and prior novel therapy did not impact outcomes. In our study, HCT resulted in durable remissions in therapy-sensitive patients with DLBCL-RS treated in the era of targeted CLL/SLL therapy, including patients with high-risk features.
CGRP outflow into jugular blood and cerebrospinal fluid and permeance for CGRP of rat dura mater
Authors: Risch Miriam , Vogler Birgit , Dux Mária , Messlinger Karl 
Published: September 2021

Abstract
Background
Calcitonin gene-related peptide (CGRP) is released from activated meningeal afferent fibres in the cranial dura mater, which likely accompanies severe headache attacks. Increased CGRP levels have been observed in different extracellular fluid compartments during primary headaches such as migraine but it is not entirely clear how CGRP is drained from the meninges.

Methods
We have used an in vivo preparation of the rat to examine after which time and at which concentration CGRP applied onto the exposed parietal dura mater appears in the jugular venous blood and the cerebrospinal fluid (CSF) collected from the cisterna magna. Recordings of meningeal (dural) and cortical (pial) blood flow were used to monitor the vasodilatory effect of CGRP. In a new ex vivo preparation we examined how much of a defined CGRP concentration applied to the arachnoidal side penetrates the dura. CGRP concentrations were determined with an approved enzyme immunoassay.

Results
CGRP levels in the jugular plasma in vivo were slightly elevated compared to baseline values 5-20 min after dural application of CGRP (10 μM), in the CSF a significant three-fold increase was seen after 35 min. Meningeal but not cortical blood flow showed significant increases. The spontaneous CGRP release from the dura mater ex vivo was above the applied low concentration of 1 pM. CGRP at 1 nM did only partly penetrate the dura.

Conclusions
We conclude that only a small fraction of CGRP applied onto the dura mater reaches the jugular blood and, in a delayed manner, also the CSF. The dura mater may constitute a barrier for CGRP and limits diffusion into the CSF of the subarachnoidal space, where the CGRP concentration is too low to cause vasodilatation.
Urethral meatus preserving ventral onlay augmentation urethroplasty for female urethral stricture: our technique with initial experience
Authors: Katiyar Varun Kumar , Sood Rajeev , Singla Anurag , Goel Hemant Kumar , Khattar Nikhil , Gunavanthe Varun 
Published: September 2021

Abstract
Background
Female urethral stricture (FUS) is an uncommon cause of lower urinary tract symptoms (LUTS) in women. Reconstructive techniques are being increasingly used for strictures resistant to the more conservative form of management. Most forms of reconstruction require cutting open of urethral meatus, thereby resulting in some loss of the meatus function. We hereby describe the technique of urethral meatus sparing ventral onlay mucosal graft augmentation urethroplasty with our initial experience.

Methods
We performed this procedure in 10 cases of FUS with normal meatus and prospectively studied the outcomes over a period of 6 months follow-up.

Results
There was 90 percent success rate with one recurrence. The mean Qmax increased from 7.2 to 19.5 ml/s, mean post-void residual urine (PVRU) decreased from 96.5 to 22.7 ml and the mean IPSS decreased from 26.1 to 5.7. There were no major complications noted and the patients demonstrated significant subjective and objective improvement of symptoms in the follow-up period.

Conclusion
The technique of meatus sparing ventral onlay augmentation graft urethroplasty is a promising approach with good outcomes, is reproducible and has minimal complication rate.
Education of the primary health care staff based on acceptance and commitment therapy is associated with reduced sick leave in a prospective controlled trial
Authors: Kadowaki Åsa , Alvunger Anna-Karin , Larsen Hanna Israelsson , Persdotter Anna , Zak Marta Stelmach , Johansson Peter , Nystrom Fredrik H. 
Published: September 2021

Abstract
Background
The use of cognitive behavioral therapy (CBT) to cope with mental distress and pain issues has helped many patients in primary health care in Sweden. However, the effects of CBT to reduce sick leave has not been equally convincing. Acceptance and Commitment Therapy (ACT) is an evolution of traditional CBT and we aimed to study if education based on ACT of the staff rather than the patients could reduce sick leave in primary health care.

Methods
This was a prospective trial in 6 primary health care centers in Kalmar (total amount of registered subjects of 28,930) in which the staff (physicians, nurses and therapists) received group-based education according to ACT during 2018 and 2019. The effects were compared with 5 similarly sized control health care centers in the neighboring Region of Jönköping in which no such education took place. The main aim was to study changes in sick leave in the 6 primary care centers of Kalmar and to keep track of more general trends by studying sick leave also in Jönköping, letting sick leave in the year 2017 to be the reference period for both areas.

Results
The staff at the health care centers in Kalmar reported to having attended a mean of 5.2 ± 2 educational ACT-sessions with psychiatrist Kadowaki in Kalmar. Sick leave for ICD-10 F43 (reaction to severe stress and related adjustment-disorders) was reduced from a mean value of 28.7 ± 9.1ongoing sick leaves/month in 2017 to 22.6 ± 7.0 sick leaves/month in 2018 (-21%, p = 0.033) and to 18.1 ± 10 sick leaves/month in 2019 (-37%, p = 0.038). The corresponding sick leave for any diagnosis (total sick leave) was reduced from 132 ± 39 sick leaves/month in 2017 to 118 ± 38 sick leaves/month in 2018 (-11%, p = 0.056) and to 102 ± 37 sick leaves/month in 2019 (-21%, p = 0.021). The corresponding sick leave comparisons in the control health centers did not show any significant changes (all p-values ≥ 0.24).

Conclusions
Total monthly mean sick leave was reduced 21% in the health care centers in Kalmar during the second year of the educational ACT intervention of the staff while it was unchanged in Jönköping. This suggests a significant effect to induce a reduction in long-term sick leave for patients in primary health care in which the staff received education according to ACT. The results of this trial could serve as a basis for a randomized trial in order to ascertain causality.

Trial registration
Pre-registration November 9, 2018 on ClinicalTrials.gov with number NCT03737019.
Expert consensus on the identification, diagnosis, and treatment of neurotrophic keratopathy
Authors: Dana Reza , Farid Marjan , Gupta Preeya K. , Hamrah Pedram , Karpecki Paul , McCabe Cathleen M. , Nijm Lisa , Pepose Jay S. , Pflugfelder Stephen , Rapuano Christopher J. , Saini Arvind , Gibbs Sarah N. , Broder Michael S. 
Published: September 2021

Abstract
Background
Neurotrophic keratopathy (NK) is a relatively uncommon, underdiagnosed degenerative corneal disease that is caused by damage to the ophthalmic branch of the trigeminal nerve by conditions such as herpes simplex or zoster keratitis, intracranial space-occupying lesions, diabetes, or neurosurgical procedures. Over time, epithelial breakdown, corneal ulceration, corneal melting (thinning), perforation, and loss of vision may occur. The best opportunity to reverse ocular surface damage is in the earliest stage of NK. However, patients typically experience few symptoms and diagnosis is often delayed. Increased awareness of the causes of NK, consensus on when and how to screen for NK, and recommendations for how to treat NK are needed.

Methods
An 11-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on when to screen for and how best to diagnose and treat NK. Clinicians reviewed literature on the diagnosis and management of NK then rated a detailed set of 735 scenarios. In 646 scenarios, panelists rated whether a test of corneal sensitivity was warranted; in 20 scenarios, they considered the adequacy of specific tests and examinations to diagnose and stage NK; and in 69 scenarios, they rated the appropriateness of treatments for NK. Panelist ratings were used to develop clinical recommendations.

Results
There was agreement on 94% of scenarios. Based on this consensus, we present distinct circumstances when we strongly recommend or may consider a test for corneal sensitivity. We also present recommendations on the diagnostic tests to be performed in patients in whom NK is suspected and treatment options for NK.

Conclusions
These expert recommendations should be validated with clinical data. The recommendations represent the consensus of experts, are informed by published literature and experience, and may improve outcomes by helping improve diagnosis and treatment of patients with NK.
Depression and its associated factors: perceived stress, social support, substance use and related sociodemographic risk factors in medical school residents in Nairobi, Kenya
Authors: Shah Sayed Shah Nur Hussein , Laving Ahmed , Okech-Helu Violet Caroline , Kumar Manasi 
Published: September 2021

Abstract
Background
Little data exists regarding depression and its associated factors in medical residents and doctors in Sub-Saharan Africa. Residents are at high risk of developing depression owing to the stressful nature of their medical practice and academic training. Depression in medical residents leads to decreased clinical efficiency, and poor academic performance; it can also lead to substance abuse and suicide. Our primary aim was to measure depression prevalence among medical residents in Kenya’s largest national teaching and referral hospital. Secondary aims were to describe how depression was associated with perceived stress, perceived social support, substance use, and educational environment.

Methods
We sampled 338 residents belonging to 8 different specialties using self administered questionnaires in this cross-sectional survey between October 2019 and February 2020. Questionnaires included: sociodemographics, the Centres for Epidemiology Depression Scale - Revised, Perceived Stress Scale, Multidimensional Scale of Perceived Social Support, Alcohol, Smoking and Substance Involvement Screening Test, and Postgraduate Hospital Educational Environment Measure. Bivariate and multivariate linear regression were used to assess for risk factors for depression.

Results
Mean participant age was 31.8 years and 53.4% were males. Most residents (70.4%) reported no to mild depressive symptoms, 12.7% had moderate, and 16.9% had severe depressive symptoms. Most residents had high social support (71.8%) and moderate stress (61.6%). The educational environment was rated as more positive than negative by 46.3% of residents. Bivariate analyses revealed significant correlations between depressive symptoms, perceived stress, substance use, perceived social support, and educational environment. Multivariate analysis showed that depression was strongly associated with: fewer hours of sleep (β = − 0.683, p = 0.002), high perceived stress (β = 0.709, p < 0.001) and low perceived social support (β = − 2.19, p < 0.001).

Conclusions
Only 30% of medical residents in our study had moderate and severe depressive symptoms. Most residents in our study reported high levels of social support, and moderate levels of stress. Though their overall appraisal of medical residency experience was positive, mental health support and self-care skills in the training of medical professionals needs prioritization.
Mid-Term outcomes following fresh-frozen humeral head osteochondral allograft reconstruction for reverse Hill Sachs lesion: a case series
Authors: Marcheggiani Muccioli Giulio Maria , Rinaldi Vito Gaetano , Lullini Giada , Ritali Alice , Mosca Massimiliano , Romagnoli Matteo , Guerra Enrico , Zaffagnini Stefano 
Published: September 2021

Abstract
Background
Locked posterior glenohumeral dislocations with a reverse Hill-Sachs impaction fracture involving less than 30% of the humeral head are most frequently treated with lesser tuberosity transfer into the defect, whereas those involving more than 50% undergo humeral head arthroplasty. Reconstruction of the defect with segmental femoral osteochondral allografts has been proposed to treat patients between these two ranges, but the medium−/long-term outcomes of this joint-preserving procedure are controversial.

Methods
Between 2001 and 2018, 12 consecutive patients with a unilateral locked posterior shoulder dislocation and an impaction fracture from 30 to 50% (mean 31% ± 1.32) of the humeral head were treated with segmental reconstruction of the defect with fresh-frozen humeral head osteochondral allografts. Patients were assessed clinically, radiographically and with computed tomography (CT) at a medium follow-up of 66 ± 50.25 months (range, 24–225).

Results
All twelve shoulders presented a slight limitation in anterior elevation (average, 166.6° ± 22.76). The mean active external rotation with the shoulder at 90° of abduction was 82.5° ± 6.61, and that with the arm held in stable adduction was 79.16 ± 18.80. The mean abduction was 156.25° ± 25.09.
The mean Constant-Murley score (CS) was 82 ± 15.09 points (range, 40–97 points), and the mean ASES was 94 ± 8.49 points. The mean pre- and postoperatively Western Ontario Shoulder Instability index (WOSI) was 236.5 ± 227.9 and 11.20 ± 10.85, respectively.
Development of osteoarthrosis (OA) was minimal. The average allograft resorption rate was 4% ± 2.4. There were no cases of failure (reoperation for any reason) in this series.

Conclusion
Segmental humeral head reconstruction with humeral head fresh-frozen osteochondral allografts provides good to excellent clinical results with low-grade OA and low allograft resorption in patients with locked posterior shoulder dislocation.

Trial registration
ClinicalTrials.gov PRS, ClinicalTrials.gov ID: NCT04823455. Registered 29 March 2021 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AU8P&selectaction=Edit&uid=U0004J36&ts=12&cx=6cykp8

Level of evidence
Level IV, Case Series, Treatment Study.
Evaluation of intra-ovarian platelet-rich plasma administration on oocytes-dependent variables in patients with poor ovarian response: A retrospective study according to the POSEIDON criteria
Authors: Farimani Marzieh , Nazari Arash , Mohammadi Shahrzad , Anvari Aliabad Roghayeh 
Published: September 2021

Abstract
Background
Poor ovarian response (POR) is among the common findings in infertile women with no significant underlying condition. The aim of this study was to investigate the intra-ovarian potential of platelet-rich plasma (PRP) administration on oocytes-dependent variables in the POR women grouped according to the POSEIDON criteria.

Methods
This retrospective study was performed on POR women with no underlying condition who have undergone intra-ovarian PRP injection. As well as patients’ age, the number of total and MI, MII, and GV oocytes were extracted from the files. The laboratory variables including anti-mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were also gathered. In order to reduce any bias due to the possible differences in kits or devices, a single laboratory with the highest number of cases was selected and others were excluded from the study. Then, the included cases were grouped into four according to the POSEIDON criteria and analyzed for the mentioned variables by SPSS, version 25. The statistical significance level was set as P-value < 0.05.

Results
From 383 cases, a total number of 96 women were enrolled in this study. According to the POSEIDON criteria, group 4 (Age ≥ 35 years, AMH < 1.2 ng/mL) with the ratio of 56/96 (58.3%) had the highest prevalence among others. As the analyses showed, changes in the laboratory variables (LH, FSH, AMH, and estradiol) were not significant in almost all the groups following the intervention. Regarding the total oocytes number, PRP administration caused a significant increase in the total number in all the groups (all P < 0.05). Also, the number of MII oocytes was significantly increased following the treatment in all groups except for group 2 (Age ≥ 35 years, AMH ≥ 1.2 ng/mL; all P < 0.05). Of 96 cases, 14 (14.6%) got clinically pregnant following assisted reproductive techniques which this number were significantly differed among the groups (P = 0.002).

Conclusion
This study showed that PRP treatment was effective on total and MII oocyte numbers in the patients with POR, however, further studies are required.
Effects of a three-armed randomised controlled trial using self-monitoring of daily steps with and without counselling in prediabetes and type 2 diabetes—the Sophia Step Study
Authors: Rossen Jenny , Larsson Kristina , Hagströmer Maria , Yngve Agneta , Brismar Kerstin , Ainsworth Barbara , Åberg Linda , Johansson Unn-Britt 
Published: September 2021

Abstract
Background
This aimed to evaluate the effects of self-monitoring of daily steps with or without counselling support on HbA1c, other cardiometabolic risk factors and objectively measured physical activity (PA) during a 2-year intervention in a population with prediabetes or type 2 diabetes.

Methods
The Sophia Step Study was a three-armed parallel randomised controlled trial. Participants with prediabetes or type 2 diabetes were recruited in a primary care setting. Allocation (1:1:1) was made to a multi-component intervention (self-monitoring of steps with counselling support), a single-component intervention (self-monitoring of steps without counselling support) or standard care. Data were collected for primary outcome HbA1c at baseline and month 6, 12, 18 and 24. Physical activity was assessed as an intermediate outcome by accelerometer (ActiGraph GT1M) for 1 week at baseline and the 6-, 12-, 18- and 24-month follow-up visits. The intervention effects were evaluated by a robust linear mixed model.

Results
In total, 188 subjects (64, 59, 65 in each group) were included. The mean (SD) age was 64 (7.7) years, BMI was 30.0 (4.4) kg/m2 and HbA1c was 50 (11) mmol/mol, 21% had prediabetes and 40% were female. The dropout rate was 11% at 24 months. Effect size (CI) for the primary outcome (HbA1c) ranged from -1.3 (-4.8 to 2.2) to 1.1 (-2.4 to 4.6) mmol/mol for the multi-component vs control group and from 0.3 (-3.3 to 3.9) to 3.1 (-0.5 to 6.7) mmol/mol for the single-component vs control group. Effect size (CI) for moderate-to-vigorous physical activity ranged from 8.0 (0.4 to 15.7) to 11.1 (3.3 to 19.0) min/day for the multi-component vs control group and from 7.6 (-0.4 to 15.6) to 9.4 (1.4 to 17.4) min/day for the single-component group vs control group.

Conclusion
This 2-year intervention, including self-monitoring of steps with or without counselling, prevented a decrease in PA but did not provide evidence for improved metabolic control and cardiometabolic risk factors in a population with prediabetes or type 2 diabetes.

Trial registration
ClinicalTrials.gov, NCT02374788. Registered 2 March 2015—Retrospectively registered.