bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced expression of mitochondrial fumarate hydratase in progressive multiple sclerosis contributes to impaired in vitro mesenchymal stromal cell-mediated neuroprotection
Authors: Sarkar Pamela , Redondo Juliana , Hares Kelly , Bailey Steven , Georgievskaya Anastasia , Heesom Kate , Kemp Kevin C , Scolding Neil J , Rice Claire M 
Published: November 2021

Background: Cell-based therapies for multiple sclerosis (MS), including those employing autologous bone marrow-derived mesenchymal stromal cells (MSC) are being examined in clinical trials. However, recent studies have identified abnormalities in the MS bone marrow microenvironment. Objective: We aimed to compare the secretome of MSC isolated from control subjects (C-MSC) and people with MS (MS-MSC) and explore the functional relevance of findings. Methods: We employed high throughput proteomic analysis, enzyme-linked immunosorbent assays and immunoblotting, as well as in vitro assays of enzyme activity and neuroprotection. Results: We demonstrated that, in progressive MS, the MSC secretome has lower levels of mitochondrial fumarate hydratase (mFH). Exogenous mFH restores the in vitro neuroprotective potential of MS-MSC. Furthermore, MS-MSC expresses reduced levels of fumarate hydratase (FH) with downstream reduction in expression of master regulators of oxidative stress. Conclusions: Our findings are further evidence of dysregulation of the bone marrow microenvironment in progressive MS with respect to anti-oxidative capacity and immunoregulatory potential. Given the clinical utility of the fumaric acid ester dimethyl fumarate in relapsing–remitting MS, our findings have potential implication for understanding MS pathophysiology and personalised therapeutic intervention.
The ethical and medico-legal challenges of telemedicine in the coronavirus disease 2019 era: A comparison between Egypt and India
Authors: Ghitani Sara A , Ghanem Maha A , Alhoshy Hanaa S , Singh Jaskran , Awasthi Supriya , Kaur Ekampreet 
Published: November 2021

Background In the coronavirus disease 2019 era, doctors have tried to decrease hospital visits and admissions. To this end, telemedicine was implemented in a non-systematic manner according. The objective of this study was to assess the current knowledge and attitudes of physicians in Alexandria, Egypt, and Punjab, India, toward telemedicine and its ethical and medico-legal issues. Method A cross-sectional study was implemented using an anonymous self-administered questionnaire carried out over two months (July and August 2020). A four-point Likert scale was used to collect data about background knowledge, training in telemedicine and ethical and medico-legal issues in telemedicine practice. Results The questionnaire was completed by 175 Egyptian and 51 Indian physicians from different specialties. A significantly higher percentage of Indian physicians practiced telemedicine than Egyptian physicians during the coronavirus disease 2019 era. Although most physicians had no specific training or licensing to practice telemedicine, most of them practiced telemedicine through their social media accounts. Ethical violations involving waiving patient consent were detected. Significant ethical violations to doctors, for example, blackmail, defamation, hate speech, accusations in a court and violations of privacy, were observed. Indian physicians (39.2%) and Egyptian physicians (24%) thought the penalties should be lower in telemedicine than in traditional practice. Finally, most participants would like to continue using telemedicine after the coronavirus disease 2019 era but with improvements. Conclusions Coronavirus disease 2019 changed the acceptance of telemedicine by physicians. Many ethical and legal issues need to be addressed and clarified using formal training before implementation and standardization of telemedicine services.
Clinical presentation and maternal-fetal outcomes of Mirror Syndrome: A case series of 10 affected pregnancies
Authors: Mogharbel Hussain , Hunt Jennifer , D’Souza Rohan , Hobson Sebastian R 
Published: November 2021

Background Mirror Syndrome, also known as Ballantyne syndrome, is a rare condition with fewer than 120 cases described in the literature. A simultaneous edematous state of the mother, fetus and placenta is pathognomonic, with the maternal condition frequently presenting with signs and symptoms similar to that of preeclampsia. Objective Our aim was to add to the international body of literature through identification of all cases of Mirror Syndrome at two Canadian tertiary obstetric centres and characterize the maternal presentation, laboratory findings, and perinatal outcomes. Methodology We performed a retrospective chart review of all cases of fetal hydrops from two tertiary centres in Winnipeg (Manitoba, Canada) between 2000 and 2019. There were 276 cases of fetal hydrops during this period, of which 10 cases satisfied the diagnostic criteria for Mirror Syndrome where maternal and perinatal outcomes were analysed. Results The median gestational age at diagnosis with Mirror Syndrome was 23 weeks and 3 days of gestation and at birth was 25 weeks and 0 days of gestation. The majority of women were multiparous (80%) and had elevated maternal body mass index (median 33 kg/m2). The most common maternal clinical findings included weight gain (100%) and hypertension (90%). The most common laboratory findings included low hematocrit (100%), hypoalbuminemia (80%), anemia (70%) and hyperuricemia (70%). Structural anomalies were observed in 50% of cases, over half of the fetuses were stillborn (66.7%) and one quarter of pregnancies resulted in neonatal deaths (25%). The median time until maternal improvement of Mirror Syndrome was 2 days postpartum. Conclusion Mirror Syndrome affected 3.6% of all cases of fetal hydrops in our cohort, and showed associations with multiparity, elevated BMI, hemodilution, hypoalbuminemia, anemia and hyperuricemia. Delivery is frequently required for fetal and/or maternal indications and symptoms usually improved rapidly after delivery.
Treatment patterns, testing practices, and outcomes in the pre-FLAURA era for patients with EGFR mutation-positive advanced NSCLC: a retrospective chart review (REFLECT)
Authors: Addeo Alfredo , Hochmair Maximilian , Janzic Urska , Dudnik Elizabeth , Charpidou Andriani , Płużański Adam , Ciuleanu Tudor , Donev Ivan Shterev , Elbaz Judith , Aarøe Jørgen , Ott René , Peled Nir 
Published: November 2021

Introduction: For epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line (1 L) treatment in the advanced setting. Osimertinib, a third-generation EGFR-TKI, received full approval in 2017 for second-line (2 L) treatment of EGFR T790M-positive NSCLC. The REFLECT study characterizes real-world treatment/testing patterns, attrition rates, and outcomes in patients with EGFRm advanced NSCLC treated with 1 L first-/second-generation (1G/2G) EGFR-TKIs before 1 L osimertinib approval. Methods: Retrospective chart review (NCT04031898) of European/Israeli adults with EGFRm unresectable locally advanced/metastatic NSCLC, initiating 1 L 1G/2G EGFR-TKIs 01/01/15–30/06/18 (index date). Results: In 896 patients (median follow-up of 21.5 months), the most frequently initiated 1 L EGFR-TKI was afatinib (45%). Disease progression was reported in 81%, including 10% (86/896) who died at 1 L. By the end of study, most patients discontinued 1 L (85%), of whom 33% did not receive 2 L therapy. From index, median 1 L real-world progression-free survival was 13.0 (95% confidence interval (CI): 12.3–14.1) months; median overall survival (OS) was 26.2 (95% CI: 23.6–28.4) months. 71% of patients with 1 L progression were tested for T790M; 58% were positive. Of those with T790M, 95% received osimertinib in 2 L or later. Central nervous system (CNS) metastases were recorded in 22% at index, and 15% developed CNS metastases during treatment (median time from index 13.5 months). Median OS was 19.4 months (95% CI: 17.1–22.1) in patients with CNS metastases at index, 24.8 months (95% CIs not available) with CNS metastases diagnosed during treatment, and 30.3 months (95% CI: 27.1, 33.8) with no CNS metastases recorded. Conclusion: REFLECT is a large real-world study describing treatment patterns prior to 1 L osimertinib availability for EGFRm advanced NSCLC. Given the attrition rates highlighted in the study and the impact of CNS progression on outcomes, offering a 1 L EGFR-TKI with CNS penetration may improve patient outcomes in this treatment setting.
A Real-World Analysis of High-Frequency 10 kHz Spinal Cord Stimulation for the Treatment of Painful Diabetic Peripheral Neuropathy
Authors: Chen Jeffrey L. , Hesseltine Andrew W. , Nashi Sara E. , Sills Shawn M. , McJunkin Tory L. , Patil Sandeep , Bharara Manish , Caraway David L. , Brooks Elizabeth S. 
Published: November 2021

Background: Diabetes is one of the most prevalent chronic health conditions and diabetic neuropathy one of its most prevalent and debilitating complications. While there are treatments available for painful diabetic peripheral neuropathy (pDPN), their effectiveness is limited. Method: This retrospective, multi-center, real-world review assessed pain relief and functional improvements for consecutive patients with diabetic neuropathy aged ≥18 years of age who were permanently implanted with a high-frequency (10 kHz) spinal cord stimulation (SCS) device. Available data were extracted from a commercial database. Results: In total 89 patients consented to being included in the analysis. Sixty-one percent (54/89) of participants were male and the average age was 64.4 years (SD = 9.1). Most patients (78.7%, 70/89) identified pain primarily in their feet or legs bilaterally. At the last assessment, 79.5% (58/73) of patients were treatment responders, defined as having at least 50% patient-reported pain relief from baseline. The average time of follow-up was 21.8 months (range: 4.3 to 46.3 months). A majority of patients reported improvements in sleep and overall function relative to their baseline. Conclusions: This real-world study in typical clinical practices found 10 kHz SCS provided meaningful pain relief for a substantial proportion of patients refractory to current pDPN management, similar to published literature. This patient population has tremendous unmet needs and this study helps demonstrate the potential for 10 kHz SCS to provide an alternative pain management approach.
Effects of Acute Alcohol Intake on Nasal Patency
Authors: Deng Yuzhoujia , Wang Chengshuo , Shen Shen , Yang Xiaozhe , Lou Hongfei , Zhang Luo 
Published: November 2021

Background Acute alcohol intake may influence nasal patency; however, there is lack of objective evidence. Objective The aim of this study was to evaluate the effects of acute alcohol intake on nasal patency employing both subjective and objective measures. Methods A total of 31 participants were classified into 2 groups of non-heavy drinkers (n = 17) and heavy drinkers (n = 14). Both groups consumed wine in 1 h and were assessed for subjective nasal symptoms and objective nasal patency, using rhinomanometry and acoustic rhinometry, at baseline and at 0.5, 2, and 6 h post-alcohol consumption. Results Alcohol consumption significantly increased nasal obstruction from baseline values in both heavy and non-heavy drinking groups. Total nasal volume (TNV) and the minimal cross-sectional area (MCA) were significantly decreased and nasal airway resistance (NAR) significantly increased from baseline values by 2 h post-alcohol consumption for both heavy and non-heavy drinking groups ( P < .05). Significant differences were found in TNV, MCA, and NAR between baseline and post-drinking in allergic rhinitis subjects; with no significant differences in MCA and NAR in subjects without allergic rhinitis. Pulse rate (PR) and temperature (T) were elevated, and blood pressure (BP) was decreased after alcohol consumption ( P < .05). Blood alcohol concentration (BAC) was not significantly correlated with nasal patency with regard to any subjective or objective measurement. Conclusion Acute alcohol consumption may impair nasal patency, independent of the amount consumed. Individuals with allergic rhinitis may be more prone to nasal obstruction after alcohol consumption than those without allergic rhinitis.
Identifying technology industry-led initiatives to address digital health equity
Authors: Durocher Keri , Boparai Navi , Jankowicz Damian , Strudwick Gillian 
Published: November 2021

Objective The COVID-19 pandemic has highlighted various barriers to health and the necessity of having access to digital health services. The technology industry can support addressing health barriers, promoting health equity and partnering with organizations to ensure access to digital health services for underserviced communities. The main objective of this study was to 1) identify what initiatives have been developed within the technology industry to address digital health equity; and to 2) determine whether these initiatives have been effective. Methods A rapid review and a grey literature scan were conducted. The academic searches were performed using four databases, including Ovid MEDLINE, Scopus, CINAHL and PsychInfo. Two reviewers screened the articles for inclusion criteria. The grey literature scan was performed through Google and Million Short. Searches of technology industry initiatives were completed through scanning technology companies listed on the New York Stock Exchange, the Toronto Stock Exchange and iShares Expanded Tech Sector – Exchange Traded Fund. Results Within the technology industry, 39 companies had relevant initiatives. These were identified as having one or more of the following: 1) having health-related collaborations with other companies, 2) promoting access to technology infrastructure and 3) delivering programs that supported notable inequities within the social determinants of health. Limited data are available on the effectiveness of these initiatives in reducing health inequities. Conclusions As technology in the delivery of health services continues to evolve, health equity initiatives must be supported through innovative strategies. Partnering with the technology industry may be one way of addressing these health equity challenges.
Preoperative Intra-articular Steroid Injections as Predictors of Hip Arthroscopy: 2-Year Outcomes
Authors: Mujahed Tala , Hassebrock Jeffrey D. , Makovicka Justin L. , Pollock Jordan R. , Wilcox Justin G. , Patel Karan A. , Economopoulos Kostas J. 
Published: November 2021

Background: In patients with femoroacetabular impingement, preoperative diagnostic injections are commonly used to establish a diagnosis of intra-articular pathology. In some cases, intra-articular steroid injections are also used for therapeutic purposes. Purpose/Hypothesis: The purpose of this study was to determine if a positive response to intra-articular steroid injection was predictive of superior outcomes after hip arthroscopy to determine if the response to intra-articular steroid injection was predictive of outcomes after hip arthroscopy. It was hypothesized that a positive response to a preoperative hip injection would be predictive of improved short- to midterm outcomes after hip arthroscopy. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective study of 208 patients who elected to have ultrasound-guided intra-articular steroid injection before they underwent hip arthroscopy between January 2016 and December 2016. Patients were divided into 2 groups: those who showed improvement in pain after the injection (steroid responder group) and those who showed no response (nonresponder group). The authors compared the preoperative and 2-year postoperative patient-reported outcomes (modified Harris Hip Score [mHHS] and Hip Outcome Score–Activities of Daily Living [HOS-ADL]) and radiographic findings between groups. Clinical endpoints, including rates of revision and conversion to total hip arthroplasty, were also reviewed. Results: There were 88 patients in the nonresponder group and 120 patients in the responder group, with no significant between-group differences in preoperative descriptive variables. The responder group had significantly higher 2-year mHHS and HOS-ADL, pre- to postoperative change in mHHS and HOS-ADL, percentage of patients achieving the patient acceptable symptomatic state (PASS) on the mHHS, and percentage of patients reaching the minimum clinically important difference and the PASS on the HOS-ADL. There was no difference in Tönnis grade, acetabular labrum articular disruption grade, revision rate, or conversion to total hip arthroplasty between the 2 groups. Conclusion: The response to preoperative intra-articular injection did aid in predicting 2-year patient-reported outcomes of hip arthroscopy for femoroacetabular impingement. Overall, the result of a preoperative intra-articular injection can be a helpful clinical tool for surgical decision-making and counseling patients on expected outcomes after hip arthroscopy.
LNK (SH2B3) inhibition expands healthy and Fanconi anemia human hematopoietic stem and progenitor cells
Authors: Holdreith Nicholas , Lee Grace , Chandra Vemika , Salinas Carlo Salas , Nicholas Peter , Olson Timothy S. , Tong Wei 
Published: November 2021

Abstract
Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for a variety of hematological diseases. Allogenic HSCT requires hematopoietic stem cells (HSCs) from matched donors and comes with cytotoxicity and mortality. Recent advances in genome modification of HSCs have demonstrated the possibility of using autologous HSCT-based gene therapy to alleviate hematologic symptoms in monogenic diseases, such as the inherited bone marrow failure (BMF) syndrome Fanconi anemia (FA). However, for FA and other BMF syndromes, insufficient HSC numbers with functional defects results in delayed hematopoietic recovery and increased risk of graft failure. We and others previously identified the adaptor protein LNK (SH2B3) as a critical negative regulator of murine HSC homeostasis. However, whether LNK controls human HSCs has not been studied. Here, we demonstrate that depletion of LNK via lentiviral expression of miR30-based short hairpin RNAs results in robust expansion of transplantable human HSCs that provided balanced multilineage reconstitution in primary and secondary mouse recipients. Importantly, LNK depletion enhances cytokine-mediated JAK/STAT activation in CD34+ hematopoietic stem and progenitor cells (HSPCs). Moreover, we demonstrate that LNK depletion expands primary HSPCs associated with FA. In xenotransplant, engraftment of FANCD2-depleted FA-like HSCs was markedly improved by LNK inhibition. Finally, targeting LNK in primary bone marrow HSPCs from FA patients enhanced their colony forming potential in vitro. Together, these results demonstrate the potential of targeting LNK to expand HSCs to improve HSCT and HSCT-based gene therapy.
Construction of yeast one-hybrid library and screening of transcription factors regulating LhMYBSPLATTER expression in Asiatic hybrid lilies (Lilium spp.)
Authors: Cao Yuwei , Bi Mengmeng , Yang Panpan , Song Meng , He Guoren , Wang Jing , Yang Yue , Xu Leifeng , Ming Jun 
Published: November 2021

Abstract
Background
Anthocyanins, which belong to flavonoids, are widely colored among red-purple pigments in the Asiatic hybrid lilies (Lilium spp.). Transcription factor (TF) LhMYBSPLATTER (formerly known as LhMYB12-Lat), identified as the major kernel protein, regulating the anthocyanin biosynthesis pathway in ‘Tiny Padhye’ of Tango Series cultivars, which the pigmentation density is high in the lower half of tepals and this patterning is of exceptional ornamental value. However, the research on mechanism of regulating the spatial and temporal expression differences of LhMYBSPLATTER, which belongs to the R2R3-MYB subfamily, is still not well established. To explore the molecular mechanism of directly related regulatory proteins of LhMYBSPLATTER in the anthocyanin pigmentation, the yeast one-hybrid (Y1H) cDNA library was constructed and characterized.

Results
In this study, we describe a yeast one-hybrid library to screen transcription factors that regulate LhMYBSPLATTER gene expression in Lilium, with the library recombinant efficiency of over 98%. The lengths of inserted fragments ranged from 400 to 2000 bp, and the library capacity reached 1.6 × 106 CFU of cDNA insert, which is suitable to fulfill subsequent screening. Finally, seven prey proteins, including BTF3, MYB4, IAA6-like, ERF4, ARR1, ERF WIN1-like, and ERF061 were screened by the recombinant bait plasmid and verified by interaction with the LhMYBSPLATTER promoter. Among them, ERFs, AUX/IAA, and BTF3 may participate in the negative regulation of the anthocyanin biosynthesis pathway in Lilium.

Conclusion
A yeast one-hybrid library of lily was successfully constructed in the tepals for the first time. Seven candidate TFs of LhMYBSPLATTER were screened, which may provide a theoretical basis for the study of floral pigmentation.
Bacterial and fungal profile, drug resistance pattern and associated factors of isolates recovered from blood samples of patients referred to Ethiopian Public Health Institute: cross-sectional study
Authors: Tsegaye Etsehiwot Adamu , Teklu Dejenie Shiferaw , Bonger Zelalem Tazu , Negeri Abebe Aseffa , Bedada Tesfaye Legesse , Bitew Adane 
Published: November 2021

AbstractBackgroundBlood stream infections are serious infections that usually induce prolongation of hospital stay, morbidity and mortality in several countries including Ethiopia. The aim of this study was to determine bacterial and fungal profile, their drug resistance patterns, and risk factors associated with blood stream infections.MethodsA cross sectional study design was conducted from February 23 to June 23, 2020 at Ethiopian public health. A structured questionnaire was used to collect data on socio-demographic factors and clinical conditions. Blood specimens were analyzed using standard microbiological techniques. Antimicrobial susceptibility tests were performed using Kirby–Bauer disc diffusion technique and Vitek compact 2. Simple and multiple logistic regressions were used to assess the potential risk factors.ResultsA total of 175 pathogens isolated from 346 blood specimens. Of these, 60% Gram-negative bacteria, 30.86% Gram-positive bacteria and 9.14% fungal isolates were identified.Burkholderia cepaciaandCoagulase negative staphylococcuswere the predominant pathogen among Gram-negative and Gram-positive bacteria respectively. Among fungus,Candida krusei(56.25%) was the most predominant isolate. The highest proportions of antibacterial resistance were observed among 3rd generation cephalosporin and penicillin. Most fungal isolates expressed resistance to fluconazole. Sex (P = 0.007), age (P < 0.001) and use of invasive medical devices (P = 0.003) were identified as risk factors for bacterial blood stream infections.ConclusionThe study showed high prevalence of blood stream infection was due toB. cepaciaand non-C. albicansspp. This finding alarming ongoing investigation of blood stream infection is important for recognizing future potential preventive strategies including environmental hygiene and management of comorbid medical diseases to reduce the problem.