bluuebunny/crossref_metadata_2025 huggingface dataset:
Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist
Authors: Terakawa Aiko , Chujo Daisuke , Yasuda Kazuki , Ueno Keisuke , Nakamura Tomoka , Hamano Shoko , Ohsugi Mitsuru , Tanabe Akiyo , Ueki Kohjiro , Kajio Hiroshi
Published: August 2020

Rationale:

Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA.

Patient concerns:

A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day.

Diagnosis:

She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5.

Interventions:

The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated.

Outcomes:

Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy.

Lessons:

GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.
Fetal cardiac rhabdomyoma due to paternal mosaicism of TSC2
Authors: Chen Lin , Jiang Yu , Wang Jing
Published: August 2020

Rationale:

Rhabdomyoma is the most common type of fetal heart tumors and 50% to 60% of cardiac rhabdomyomas are associated with tuberous sclerosis complex (TSC). TSC is characterized by hamartomas in multiple organ systems including the brain, heart, skin, lungs, and kidneys, resulting in complications such as learning difficulties, epilepsy, behavioral problems, and renal failure. The etiological diagnosis of Rhabdomyoma is very important.

Patient concerns:

A 22-year-old G2P0 woman chose to terminate the pregnancy at 24 + 4 weeks of gestation because of the presence of a cardiac space-occupying lesion in the fetus.

Diagnoses:

The pathological diagnosis of cardiac neoplasm tissue was cardiac rhabdomyoma, but the etiology was unknown.

Interventions:

Targeted exome capture, next-generation sequencing (NGS) and sanger sequencing were performed on peripheral blood lymphocytes and paternal sperm.

Outcomes:

Targeted exome capture sequencing revealed a novel heterozygous variant (NM_000548, c.2294delC) in the tuberous sclerosis 2 (TSC2) gene. Sanger sequencing of maternal blood samples showed no mutation at this locus, however, suspected low level mosaicism was observed in paternal blood samples. Deep NGS analysis showed that about 7% paternal alleles from peripheral blood leucocytes and 20% paternal alleles from sperm carried the mutation consistent with somatic and germinal mosaicism.

Lessons:

For fetuses suspected of TSC, when pathogenic mutations are detected in the tuberous sclerosis 1 (TSC1) or TSC2 gene, it is recommended that the parents should be screened by deep NGS and their germ cells are screened as well if necessary, which would help to predict the risk of TSC recurrence in the next pregnancy.
Does single gene expression omnibus data mining analysis apply for only tumors and not mental illness? A preliminary study on bipolar disorder based on bioinformatics methodology
Authors: You Xu , Zhang Yunqiao , Long Qing , Liu Zijun , Feng Ziqiao , Zhang Wengyu , Teng Zhaowei , Zeng Yong
Published: August 2020

Background:

Bipolar disorder (BD), a common kind of mood disorder with frequent recurrence, high rates of additional comorbid conditions and poor compliance, has an unclear pathogenesis. The Gene Expression Omnibus (GEO) database is a gene expression database created and maintained by the National Center for Biotechnology Information. Researchers can download expression data online for bioinformatics analysis, especially for cancer research. However, there is little research on the use of such bioinformatics analysis methodologies for mental illness by downloading differential expression data from the GEO database.

Methods:

Publicly available data were downloaded from the GEO database (GSE12649, GSE5388 and GSE5389), and differentially expressed genes (DEGs) were extracted by using the online tool GEO2R. A Venn diagram was used to screen out common DEGs between postmortem brain tissues and normal tissues. Functional annotation and pathway enrichment analysis of DEGs were performed by using Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Furthermore, a protein-protein interaction network was constructed to identify hub genes.

Results:

A total of 289 DEGs were found, among which 5 of 10 hub genes [HSP90AA1, HSP90AB 1, UBE2N, UBE3A, and CUL1] were identified as susceptibility genes whose expression was downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that variations in these 5 hub genes were obviously enriched in protein folding, protein polyubiquitination, apoptotic process, protein binding, the ubiquitin-mediated proteolysis pathway, and protein processing in the endoplasmic reticulum pathway. These findings strongly suggested that HSP90AA1, UBE3A, and CUL 1, which had large areas under the curve in receiver operator curves (P < .05), were potential diagnostic markers for BD.

Conclusion:

Although there are 3 hub genes [HSP90AA1, UBE3A, and CUL 1] that are tightly correlated with the occurrence of BD, mainly based on routine bioinformatics methods for cancer-related disease, the feasibility of applying this single GEO bioinformatics approach for mental illness is questionable, given the significant differences between mental illness and cancer-related diseases.
Lymphocyte infiltration and key differentially expressed genes in the ulcerative colitis
Authors: Zhang Junhui , Shi Guixiu
Published: August 2020

Background:

Ulcerative colitis (UC) was a type of inflammatory bowel diseases, which was difficult to cure and even would malignant turn into colon cancer. The specific etiology and molecular mechanism of UC were unclear to date. The purpose of this study was to search for new targets for the diagnosis and treatment of UC.

Methods:

Firstly, we downloaded the gene expression data of UC from the gene expression omnibus database database (GSE107499), and used multiple bioinformatics methods to find differently expressed genes (DEGs) in UC. Subsequently, we evaluated the lymphocyte infiltration in UC inflamed colon tissue by using the cell type identification by estimating relative subset of known RNA transcripts method.

Results:

We obtained 1175 DEGs and 8 hub genes (IL6, TNF, PTPRC, CXCL8, FN1, CD44, IL1B, and MMP9) in this study. Among them, 903 DEGs were up-regulated and 272 DEGs were down-regulated. Compared with non-inflamed colon tissues, the inflamed colon tissues had higher levels of memory B cells, activated memory CD4+ T cells, follicular helper T cells, M1 macrophages, resting dendritic cells, activated dendritic cells, activated mast cells, and neutrophils, whereas the proportions of plasma cells, resting memory CD4+ T cells, gamma delta T cells, activated NK cells, M2 macrophages and resting mast cells were relatively lower.

Conclusions:

The DEGs, hub genes and different lymphatic infiltration conditions can provide new targets for diagnosis and treatment of UC. However, these were just predictions through some theoretical methods, and more basic experiments will be needed to prove in the future.
Is bioabsorbable screw an alternative choice for displaced medial epicondylar fractures in adolescents
Authors: Li Jin , Rai Saroj , Ze Renhao , Tang Xin , Liu Ruikang , Hong Pan
Published: August 2020

In adolescent patients, cannulated lag screw (CLS) is a widely accepted choice for fixation of the medial epicondylar fracture of the humerus (MEFH). Absorbable implants, including rod, screw, and mini-plate, have been reported in children. However, to the best of our understanding, this study is the first head-to-head comparative study of CLS versus bioabsorbable screw (BS) in the treatment of MEFH.

Patients of MEFH operated at our institute, from January 2010 to January 2016, were reviewed retrospectively. The patients were divided into 2 groups, the CLS group and the BS group, as per the type of implant the patient received. The CLS group consisted of 35 patients, whereas the BS group consisted of 30 patients. Demographic data, including sex, age at the time of surgery, operated side, and implant material, were collected from the hospital database. Elbow range of motion (ROM), radiographic manifestation was recorded during the out-patient visit. The elbow joint function was evaluated according to the Broberg and Morrey elbow scale and Mayo elbow performance index score.

Thirty patients, including 18 males and 12 females, were included in the CLS group, whereas 35 patients, including 21 males and 14 females, were included in the BS group. At 6-month follow-up, elbow range of motion, Broberg and Morrey elbow scale and Mayo elbow performance index scale showed no significant difference between the 2 groups. The carrying angle was within the normal range in both groups. There was no nonunion or malunion in either group. The rate of hypoplasia or hyperplasia was low in both groups, 3.3% in CLS and 2.9% in BS. The rate of implant prominence was significantly higher in the CLS group (33.3%) than BS (0%).

Both CLS and BS are safe and effective choices for displaced MEFH in adolescents. The BS can produce a satisfactory clinical outcome and is comparable to the CLS. Besides, the BS has the advantage of not needing second surgery for implant removal.
Computed tomography-guided coil localization for sub-fissural lung nodules
Authors: Li Er-Liang , Cao Wei , Li Yu , Zhang Miao
Published: August 2020

This study was designed to explore the safety, feasibility, and clinical efficacy of preoperative computed tomography (CT)-guided coil localization of sub-fissural lung nodules (LNs). A total of 105 LN patients underwent CT-guided coil localization followed by video-assisted thoracoscopic surgery (VATS)-guided wedge resection at our hospital from January 2016 to December 2019. Of these patients, 4 had sub-fissural LNs and were therefore subjected to trans-fissural coil localization procedures. We analyzed data pertaining to the coil localization and VATS procedures in these patients. A total of 4 coils were used to localize 4 LNs in 4 separate patients. One of these patients suffered from parenchymal hemorrhage around the needle path, while one other patient exhibited asymptomatic pneumothorax following coil localization. A thoracoscope was able to successfully visualize the coil tails in all of these patients. There were no instances of coils having been dislodged, and wedge resection was conducted with a 100% technical success rate in these patients. These 4 LNs were subsequently diagnosed as adenocarcinomas in situ (n = 3) and benign nodules (n = 1). CT-guided coil localization can be used to safely and easily localize sub-fissural LNs in patients scheduled to undergo VATS.
Effectiveness of new nerve blocks method on the articular branches of the suprascapular and subscapular nerves to treat shoulder pain
Authors: Lee Sang Hoon , Choi Hyun Hee , Lee Dong Gyu
Published: August 2020

To evaluate the effectiveness and safety of performing nerve blocks on the articular branches of the suprascapular and subscapular nerves for the treatment of shoulder pain caused by various pathologies.

Fifty-two patients with shoulder pain were included in this study. Suprascapular and subscapular nerve blocks were performed with 2.5 mL anesthetic solution (2 mL of 0.5% bupivacaine and 0.5 mL of 2 mg/mL dexamethasone). The subjects were evaluated before the procedure and 1, 3, and 6 months afterward by means of the numeric rating scale and the shoulder pain and disability index. A post-injection pain reduction of >50% and <50% was considered a positive and negative response to the blocks, respectively.

After nerve blocks, the mean numeric rating scale and shoulder pain and disability index scores were significantly reduced from pre-injection values, and this effect persisted for 6 months after injection. The positive and negative response groups consisted of 31 (60%) and 21 (40%) patients, respectively. The positive response group showed significantly better outcomes on the numeric rating scale and shoulder pain and disability index compared with the negative response group. No patients reported adverse effects either during or after the procedure.

Performing nerve blocks on the articular branches of the suprascapular and subscapular nerves resulted in positive outcomes for shoulder pain patients. Regardless of shoulder pathology, this new injection method can be safely used in shoulder pain patients.
Noninvasive Monitoring of Deep Tissue Oxygenation in Buried Flaps by Time-Resolved Near-Infrared Spectroscopy in Pigs
Authors: Lartizien Rodolphe , Planat-Chrétien Anne , Berger Michel , Henry Maxime , Coll Jean-Luc , Dot Audrey , Bettega Georges
Published: August 2020

Background:

Flap monitoring in reconstructive surgery is particularly important because flap failure is a dramatic event for the patient and for the medical team. Noninvasive deep tissue oxygenation monitoring is a challenge. The aim of this experimental study was to assess the performance of time-resolved near-infrared spectroscopy compared with continuous-wave near-infrared spectroscopy and with invasive oxygen partial pressure measurement in pigs.

Methods:

Thirty fasciocutaneous flaps based on the superficial epigastric inferior pedicle were harvested and buried under the transcutaneous dorsal muscle (approximately 1 cm thick). An optical probe was placed on the skin above each buried flap. For each pig, two buried flaps were performed, one submitted to arterial occlusion and one to venous occlusion. Oxyhemoglobin and deoxyhemoglobin concentrations were observed for over 40 minutes before clamping, almost 20 minutes during clamping and during a period of release of approximately 20 minutes. Variations in time-resolved near-infrared spectroscopy were compared to the oxygen partial pressure and continuous-wave near-infrared spectroscopy variations.

Results:

All vascular events were detected by the time-resolved near-infrared spectroscopy. During arterial clamping, oxyhemoglobin decreased rapidly, whereas deoxyhemoglobin increased moderately. The divergence of oxyhemoglobin and deoxyhemoglobin curves indicated arterial occlusion. During venous clamping, deoxyhemoglobin increased, whereas oxyhemoglobin increased briefly then remained stable or decreased moderately. The initial increases in the oxyhemoglobin and deoxyhemoglobin curves indicated venous occlusion. Oxygen partial pressure failed to detect vascular events in three cases. Continuous-wave near-infrared spectroscopy could not clearly identify vascular occlusions.

Conclusions:

Thus, the authors demonstrated the relevance of time-resolved near-infrared spectroscopy to buried flap monitoring. Time-resolved near-infrared spectroscopy could differentiate between arterial occlusion and venous occlusion.
Potential of Tissue-Engineered and Artificial Dermis Grafts for Fingertip Reconstruction
Authors: Namgoong Sik , Jung Jae Eun , Han Seung-Kyu , Jeong Seong-Ho , Dhong Eun-Sang
Published: August 2020

Background:

Management of skin and soft-tissue defects of the fingertips is functionally and aesthetically important, but controversial, especially when bones are exposed. Recent advances in wound healing technology allow the use of cells or biological dermis. The authors studied the clinical efficacy of tissue-engineered dermis grafts and artificial dermis grafts versus immediate reconstructive procedures, such as the reverse digital artery island flap, in treating bone-exposed fingertip defects.

Methods:

One hundred eighty-two patients with bone-exposed fingertip defects treated with tissue-engineered dermis grafts (n = 71), artificial dermis grafts (n = 23), or reverse digital artery island flaps (n = 88) were included in this retrospective cohort study. Surgical time, duration of hospitalization, total cost, success rate, healing time, sensory recovery, range of motion, scar quality, and patient satisfaction were compared.

Results:

No tissue-engineered or artificial dermis graft exhibited graft rejection or failure, whereas there was one partial loss and one total loss after reverse digital artery island flap surgery. Tissue-engineered dermis grafts were superior in scar quality, and artificial dermis grafts had shorter surgical times and lower surgical costs; both groups demonstrated superior results in postoperative range of motion and sensory recovery in two-point discrimination tests and shorter hospitalization, compared with the reverse digital artery island flap group. The reverse digital artery island flap had shorter complete closure time and less postoperative tingling sensation. There were no differences in overall patient satisfaction among the groups.

Conclusions:

Tissue-engineered and artificial dermis grafts may be promising alternatives for fingertip reconstruction. In particular, tissue-engineered dermis grafts may deliver superior functional results, including recovery of sensory discomfort and aesthetic results in terms of scar quality over artificial dermis grafts.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Perforator Mapping of the Profunda Artery Perforator Flap: Anatomy and Clinical Experience
Authors: Largo Rene D. , Chu Carrie K. , Chang Edward I. , Liu Jessie , Abu-Ghname Amjed , Wang Hui , Schaverien Mark V. , Mericli Alex F. , Hanasono Matthew M. , Yu Peirong
Published: August 2020

Background:

Discovering alternatives to workhorse flaps that have more consistent anatomy and lower donor-site morbidity has become a focus of reconstructive surgery research. This study provides a simplified approach to profunda artery perforator flap design and harvest based on reliable anatomical landmarks.

Methods:

A retrospective review was conducted of 70 patients who underwent 83 profunda artery perforator flap reconstructions for postoncologic defects from 2016 to 2018. The authors recorded and analyzed the profunda artery perforator flap sizes and clinical applications, the numbers and locations of the perforators, and the patient outcomes.

Results:

Most of the profunda artery perforator flaps were for head and neck [46 patients (65.7 percent)] and breast [21 patients (30 percent)] reconstructions. Flaps were most commonly based on perforator A (33.7 percent) and perforator B (33.7 percent), followed by perforators B and C combined (18.1 percent). Perforators were located a mean of 7.5 cm (perforator A), 12.7 cm (B), and 17.6 cm (C) distal to the pubic tubercle parallel to the axis between the pubic tubercle and the medial femoral condyle and 7.9 cm (A), 7.3 cm (B), and 6.1 cm (C) posterior from the axis. There was no flap loss. One patient underwent successful salvage surgery after arterial flap thrombosis. Eight patients (9.6 percent) developed superficial wound dehiscence that was managed conservatively.

Conclusions:

Perforator mapping demonstrated consistent anatomical locations of sizeable profunda artery perforators in the inner thigh. Along with its consistent and robust vascular anatomy and minimal donor-site morbidity, the profunda artery perforator flap’s volume and pliability make it a reliable option for soft-tissue reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Vulnerability to COVID-19-related Harms Among Transgender Women With and Without HIV Infection in the Eastern and Southern U.S.
Authors: Poteat Tonia C. , Reisner Sari L. , Miller Marissa , Wirtz Andrea L. ,   on behalf of the American Cohort To Study HIV Acquisition Among Transgender Women (LITE)
Published: August 2020

Background:

COVID-19 is a new pandemic, and its impact by HIV status is unknown. National reporting does not include gender identity; therefore, data are absent on the impact of COVID-19 on transgender people, including those with HIV. Baseline data from the American Cohort to Study HIV Acquisition Among Transgender Women in High Risk Areas (LITE) Study provide an opportunity to examine pre-COVID factors that may increase vulnerability to COVID-19-related harms among transgender women.

Setting:

Atlanta, Baltimore, Boston, Miami, New York City, Washington, DC.

Methods:

Baseline data from LITE were analyzed for demographic, psychosocial, and material factors that may affect vulnerability to COVID-related harms.

Results:

The 1020 participants had high rates of poverty, unemployment, food insecurity, homelessness, and sex work. Transgender women with HIV (n = 273) were older, more likely to be Black, had lower educational attainment, and were more likely to experience material hardship. Mental and behavioral health symptoms were common and did not differ by HIV status. Barriers to health care included being mistreated, provider discomfort serving transgender women, and past negative experiences; as well as material hardships, such as cost and transportation. However, most reported access to material and social support—demonstrating resilience.

Conclusions:

Transgender women with HIV may be particularly vulnerable to pandemic harms. Mitigating this harm would benefit everyone, given the highly infectious nature of this coronavirus. Collecting gender identity in COVID-19 data is crucial to inform an effective public health response. Transgender-led organizations' response to this crisis serve as an important model for effective community-led interventions.
T1-Based Synthetic Magnetic Resonance Contrasts Improve Multiple Sclerosis and Focal Epilepsy Imaging at 7 T
Authors: Massire Aurélien , Seiler Charlotte , Troalen Thomas , Girard Olivier M. , Lehmann Pierre , Brun Gilles , Bartoli Axel , Audoin Bertrand , Bartolomei Fabrice , Pelletier Jean , Callot Virginie , Kober Tobias , Ranjeva Jean-Philippe , Guye Maxime
Published: August 2020

Objectives

Ultra-high field magnetic resonance imaging (MRI) (≥7 T) is a unique opportunity to improve the clinical diagnosis of brain pathologies, such as multiple sclerosis or focal epilepsy. However, several shortcomings of 7 T MRI, such as radiofrequency field inhomogeneities, could degrade image quality and hinder radiological interpretation. To address these challenges, an original synthetic MRI method based on T1 mapping achieved with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence was developed. The radiological quality of on-demand T1-based contrasts generated by this technique was evaluated in multiple sclerosis and focal epilepsy imaging at 7 T.

Materials and Methods

This retrospective study was carried out from October 2017 to September 2019 and included 21 patients with different phenotypes of multiple sclerosis and 35 patients with focal epilepsy who underwent MRI brain examinations using a whole-body investigative 7 T magnetic resonance system. The quality of 2 proposed synthetic contrast images were assessed and compared with conventional images acquired at 7 T using the MP2RAGE sequence by 4 radiologists, evaluating 3 qualitative criteria: signal homogeneity, contrast intensity, and lesion visualization. Statistical analyses were performed on reported quality scores using Wilcoxon rank tests and further multiple comparisons tests. Intraobserver and interobserver reliabilities were calculated as well.

Results

Radiological quality scores were reported higher for synthetic images when compared with original images, regardless of contrast, pathologies, or raters considered, with significant differences found for all 3 criteria (P < 0.0001, Wilcoxon rank test). None of the 4 radiologists ever rated a synthetic image “markedly worse” than an original image. Synthetic images were rated slightly less satisfying for only 3 epileptic patients, without precluding lesion identification.

Conclusion

T1-based synthetic MRI with the MP2RAGE sequence provided on-demand contrasts and high-quality images to the radiologist, facilitating lesion visualization in multiple sclerosis and focal epilepsy, while reducing the magnetic resonance examination total duration by removing an additional sequence.
De Novo Focal and Segmental Glomerulosclerosis After COVID-19 in a Patient With a Transplanted Kidney From a Donor With a High-risk APOL1 Variant
Authors: Oniszczuk Julie , Moktefi Anissa , Mausoleo Aude , Pallet Nicolas , Malard-Castagnet Stephanie , Fourati Slim , El Karoui Khalil , Sahali Dil , Stehlé Thomas , Boueilh Anna , Verpont Marie-Christine , Matignon Marie , Buob David , Grimbert Philippe , Audard Vincent
Published: August 2020

Background.

There is compelling evidence that renal complications in a native kidney are a major concern in patients infected with severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19). The spectrum of renal lesions observed on renal grafts in this context remains to be determined.

Methods.

We report the case of a renal transplant recipient with non-severe COVID-19, who subsequently developed nephrotic syndrome associated with acute renal injury.

Results.

Renal biopsy demonstrated focal and segmental glomerulosclerosis lesions classified as not otherwise specified histological variant. Genotyping for 2 risk alleles of the apolipoprotein L1 gene demonstrated that the donor was homozygous for the G2/G2 genotype.

Conclusions.

In renal transplant patients receiving kidneys from donors with high-risk apolipoprotein L1 variants, COVID-19 may promote acute glomerular injury in the form of focal and segmental glomerulosclerosis.
Coronavirus Disease-19: Disease Severity and Outcomes of Solid Organ Transplant Recipients: Different Spectrums of Disease in Different Populations?
Authors: Ali Tariq , Al-Ali Ali , Fajji Layal , Hammad Ehab , Nazmi Ahmed , Alahmadi Ibrahim , Aleid Hassan , Ullah Asad , Shah Yaser , Broering Dieter
Published: August 2020

Background.

Coronavirus disease-19 (COVID-19) is associated with significant mortality. The elderly, patients with comorbidities, and solid organ transplant (SOT) recipients are particularly at risk. We observed a low incidence of severe disease in our population and aimed to determine the outcomes of COVID-19 (disease severity/intensive care unit [ICU] admissions/mortality) in SOT recipients.

Methods.

All SOT recipients diagnosed with COVID-19 were included. Their demographic and clinical data were recorded from the hospital electronic system. Patients were assigned to 1 of 4 stages of disease severity: stage A = asymptomatic, stage B = mild, stage C = moderate, and stage D = severe.

Results.

Of the 3052 SOT recipients, 67 were diagnosed with COVID-19. The mean age was 52 years, and 69% were male. There were approximately 25% patients in stage A, 28% in stage B, 34% in stage C, and 12% in stage D. Patients in stages C and D were older than those in stage A (P = 0.04) or stage B (P = 0.03). Lactic dehydrogenase (P < 0.01) and D-dimer (P < 0.01) levels were higher across the stages. Approximately 70% of patients were admitted for a median duration of 9 days and the median follow-up was 35 days. Acute kidney injury occurred in 19% of patients, and 45% required supplementary oxygen. The symptomatic patients were treated with Hydroxychloroquine (83%), Azithromycin (89%), and Tocilizumab (23%). Around 15% of patients were admitted to ICU and 2 patients have died.

Conclusions.

Most SOT recipients developed mild to moderate COVID-19 infection; few required ICU admission and 2 patients have died. Remaining patients have recovered and have been discharged from the hospital.
Overexpression of miR-221 stimulates proliferation of rat neural stem cell with activating Phosphatase and tensin homolog/protein kinase B signaling pathway
Authors: Chen Yanze , Gao Yunan , Lian Ying , Li Chengkun , Qu Chen , Jiang Xiaowen
Published: August 2020

Neural stem cells (NSCs) are self-renewing, multipotent cells, and remain in our brains throughout life. They could be activated by brain damage and involved in the central nervous system (CNS) repair and motor functional recovery. Previous research demonstrated that miR-221 could regulate proliferation, differentiation, and survival. However, the effect of miR-221 on NSCs remains unknown. In this study, we showed that overexpression of miR-221 inhibited the expression of phosphatase and tensin homolog (PTEN) protein and increased the phosphorylation level of protein kinase B (AKT). More importantly, an AKT-specific inhibitor abolished the effect of miR-221 on the phosphorylation level of AKT. 5-Bromo-2-deoxyUridine (BrdU) incorporation assay and Cyclin D1 expression showed that miR-221 overexpression further promoted the NSCs proliferation. However, knocking down miR-221 inhibited cell proliferation. The AKT-specific inhibitor also blocked the proliferative efficiency of miR-221. These results demonstrated that miR-221 overexpression promoted the proliferation of cultured rat NSCs, for which the PTEN/AKT pathway activation was one possible mechanism. Our research may provide a novel investigating strategy to improve stem cell treatment for CNS diseases.
Older adults exhibit greater brain activity than young adults in a selective inhibition task by bipedal and bimanual responses: an fNIRS study
Authors: Kawai Nobuyuki , Nakata Ryuzaburo , Kubo-Kawai Namiko
Published: August 2020

Inhibitory deficits are one of the predominant causes of cognitive aging. This study examined age-related changes in response inhibition. In this study, young and older participants performed a bimanual/bipedal response inhibition task while we measured their brain activity via functional near-infrared spectroscopy. Participants performed most trials bimanually (bipedally). However, they had to occasionally cancel both responses [Stop/Stop (SS) trials] or the response of one hand/foot while responding with the other [Go/Stop (GS) trials]. The participants produced more errors in the selective (GS) than in the nonselective canceling trials (SS), and in by-foot response more than in by-hand response trials, irrespective of their age. However, older participants made more errors in the selective cancelation (GS) trials and by-foot responses than young participants did. Older participants showed more frontal brain activity than young participants. The GS trials triggered more activity in the frontal brain areas than the SS trials irrespective of age at many channels, while older participants recruited more brain activation in the GS trials than in the SS trials compared to young participants. Overall, older participants exhibited higher activity in the right, middle, and inferior frontal gyrus than did young participants when performing selective and nonselective inhibition response. These results suggest that neural activation of the core inhibition network declines with age and that compensational recruitment of additional networks is used to yield an expanded inhibition circuit.
Combined-evidence analyses of ultraconserved elements and morphological data: an empirical example in iguanian lizards
Authors: Scarpetta Simon G.
Published: August 2020

Genomic datasets generated by next-generation sequencing are increasingly prevalent in phylogenetics, but morphological data are required to phylogenetically place fossils, corroborate molecular hypotheses and date phylogenies. Combined-evidence analyses provide an integrative assessment of tree topology. However, no attempt has been made to simultaneously analyse next-generation genomic datasets and morphological data, and the future of morphology in the context of genomic data is uncertain. I conducted combined-evidence analyses that include genomic and morphological datasets, specifically, with ultraconserved elements and two morphological matrices. In unweighted maximum-likelihood and Bayesian combined-evidence analyses, morphological signal was dwarfed by the ultraconserved elements, and some node support values were reduced relative to ultraconserved element-only analyses. Increasing the weight of morphological characters allowed those data to influence the tree, but weighting subjectivity should be considered in future analyses. More attempts should be made to simultaneously analyse genomic and morphological datasets.
Group living facilitates the evolution of duets in barbets
Authors: Soma Masayo , Brumm Henrik
Published: August 2020

The duets of birds have intrigued biologists for a long time, yet much remains unknown about the evolution of these striking collective displays. This is partly because previous studies on duet evolution have been biased to songbirds and neglected other bird groups. In songbirds, the absence of migration has been found to predict the occurrence of duetting, indirectlysupporting the idea that duet communication is linked with pair bonding. Here, we used phylogenetic comparative analyses in a sedentary clade of non-songbirds, the barbets (Capitonidae), to reveal new correlates of duet evolution. We found (i) that duets evolved several times independently in different barbet lineages and (ii) that duetting evolved in association with group living (i.e. the presence of helpers or non-breeding adults during the breeding period), but not with sexual monochromatism or habitat type. Our findings are consistent with a duet function in mate guarding and dominance against subordinate group members as well as joint territory defence. Altogether, the results highlight the importance of the social environment for the evolution of collective signalling.
Accelerated landings in stingless bees are triggered by visual threshold cues
Authors: Tichit Pierre , Alves-dos-Santos Isabel , Dacke Marie , Baird Emily
Published: August 2020

Most flying animals rely primarily on visual cues to coordinate and control their trajectory when landing. Studies of visually guided landing typically involve animals that decrease their speed before touchdown. Here, we investigate the control strategy of the stingless beeScaptotrigona depilis, which instead accelerates when landing on its narrow hive entrance. By presenting artificial targets that resemble the entrance at different locations on the hive, we show that these accelerated landings are triggered by visual cues. We also found thatS. depilisinitiated landing and extended their legs when the angular size of the target reached a given threshold. Regardless of target size, the magnitude of acceleration was the same and the bees aimed for the same relative position on the target suggesting thatS. depilisuse a computationally simple but elegant ‘stereotyped' landing strategy that requires few visual cues.
Structure-based Hamiltonian model for IsiA uncovers a highly robust pigment–protein complex
Authors: Schoffman Hanan , Brown William M. , Paltiel Yossi , Keren Nir , Gauger Erik M.
Published: August 2020

The iron stress-induced protein A (IsiA) is a source of interest and debate in biological research. The IsiA supercomplex, binding over 200 chlorophylls, assembles in multimeric rings around photosystem I (PSI). Recently, the IsiA–PSI structure from
Synechocystis
sp. PCC 6803 was resolved to 3.48 Å. Based on this structure, we created a model simulating a single excitation event in an IsiA monomer. This model enabled us to calculate the fluorescence and the localization of the excitation in the IsiA structure. To further examine this system, noise was introduced to the model in two forms—thermal and positional. Introducing noise highlights the functional differences in the system between cryogenic temperatures and biologically relevant temperatures. Our results show that the energetics of the IsiA pigment–protein complex are very robust at room temperature. Nevertheless, shifts in the position of specific chlorophylls lead to large changes in their optical and fluorescence properties. Based on these results, we discuss the implication of highly robust structures, with potential for serving different roles in a context-dependent manner, on our understanding of the function and evolution of photosynthetic processes.
Multi-model forecasts of the ongoing Ebola epidemic in the Democratic Republic of Congo, March–October 2019
Authors: Roosa Kimberlyn , Tariq Amna , Yan Ping , Hyman James M. , Chowell Gerardo
Published: August 2020

The 2018–2020 Ebola outbreak in the Democratic Republic of the Congo is the first to occur in an armed conflict zone. The resulting impact on population movement, treatment centres and surveillance has created an unprecedented challenge for real-time epidemic forecasting. Most standard mathematical models cannot capture the observed incidence trajectory when it deviates from a traditional epidemic logistic curve. We fit seven dynamic models of increasing complexity to the incidence data published in the World Health Organization Situation Reports, after adjusting for reporting delays. These models include a simple logistic model, a Richards model, an endemic Richards model, a double logistic growth model, a multi-model approach and two sub-epidemic models. We analyse model fit to the data and compare real-time forecasts throughout the ongoing epidemic across 29 weeks from 11 March to 23 September 2019. We observe that the modest extensions presented allow for capturing a wide range of epidemic behaviour. The multi-model approach yields the most reliable forecasts on average for this application, and the presented extensions improve model flexibility and forecasting accuracy, even in the context of limited epidemiological data.
Young bumblebees may rely on both direct pollen cues and early experience when foraging
Authors: Ruedenauer Fabian A. , Sydow David , Spaethe Johannes , Leonhardt Sara D.
Published: August 2020

An adequate supply of macro- and micronutrients determines health and reproductive success in most animals. Many bee species, for example, collect nectar and pollen to satisfy their demands for carbohydrates, protein and fat, respectively. Bees can assess the quality of pollen by feeding on it, but also pre-digestively by means of chemotactile assessment. Whether they additionally use larval nutritional experience, as has been shown for
Drosophila melanogaster
and
Bombyx mori
, is unknown. In this study, we tested whether pollen selection of bumblebee foragers is affected by nutritional experience (acquired before the onset of foraging) or solely by food quality. Bumblebee larvae were fed with one out of three different pollen blends. As adults, they were offered all three blends when they started foraging for the first time. We found all treatment groups to prefer one out of the three blends. This blend provided the highest nutritional quality and increased the bees' lifespan, as shown by feeding studies with microcolonies. Besides, bees also chose the pollen blend fed during their larval stage more often than expected, indicating a significant effect of pre-foraging experience on adult pollen foraging behaviour. The combination of both direct pollen quality assessment and pre-foraging experience (i.e. during the larval phase or as early imagines) seems to allow foraging bumblebees to efficiently select the most suitable pollen for their colony.
Chest X-ray image analysis and classification for COVID-19 pneumonia detection using Deep CNN
Authors: Gao Terry , Wang Grace
Published: August 2020

In order to speed up the discovery of COVID-19 disease mechanisms, this research developed a new diagnosis platform using deep convolutional neural network (CNN) which is able to assist radiologists with diagnosis by distinguishing COVID-19 pneumonia from non-COVID-19 pneumonia in patients at Middlemore Hospital based on chest X-rays classification and analysis. Such a tool can save time in interpreting chest X-rays and increase the accuracy and thereby enhance our medical capacity for detection and diagnosis COVID-19. The research idea is that a set of X-ray medical lung images (which include normal, infected by bacteria, infected by virus including COVID-19) were used to train a deep CNN which can be able to distinguish between the noise and the useful information and then uses this training to interpret new images by recognizing patterns that indicate certain diseases such as coronavirus infection in the individual images. The supervised learning method is used as the process of learning from the training dataset can be thought of as a doctor supervising the learning process. It becomes more accurate as the number of analyzed images growing. In this way, it imitates the training for a doctor, but the theory is that since it is capable of learning from a far larger set of images than any human, can have the potential of being more accurate.
Meta-analysis of 208,370 East Asians identifies 113 genomic loci and yields new non-immune cell relevant biological insights for systemic lupus erythematosus
Authors: Yin Xianyong , Kim Kwangwoo , Suetsugu Hiroyuki , Bang So-Young , Wen Leilei , Koido Masaru , Ha Eunji , Liu Lu , Sakamoto Yuma , Jo Sungsin , Leng Rui-Xue , Otomo Nao , Laurynenka Viktoryia , Kwon Young-Chang , Sheng Yujun , Sugano Nobuhiko , Hwang Mi Yeong , Li Weiran , Mukai Masaya , Yoon Kyungheon , Cai Minglong , Ishigaki Kazuyoshi , Chung Won Tae , Huang He , Takahashi Daisuke , Lee Shin-Seok , Wang Mengwei , Karino Kohei , Shim Seung-Cheol , Zheng Xiaodong , Miyamura Tomoya , Kang Young Mo , Ye Dongqing , Nakamura Junichi , Suh Chang-Hee , Tang Yuanjia , Motomura Goro , Park Yong-Beom , Ding Huihua , Kuroda Takeshi , Choe Jung-Yoon , Li Chengxu , Niiro Hiroaki , Park Youngho , Shen Changbing , Miyamoto Takeshi , Ahn Ga-Young , Fei Wenmin , Takeuchi Tsutomu , Shin Jung-Min , Li Keke , Kawaguchi Yasushi , Lee Yeon-Kyung , Wang Yongfei , Amano Koichi , Yang Wanling , Tada Yoshifumi , Yamaji Ken , Shimizu Masato , Atsumi Takashi , Suzuki Akari , Sumida Takayuki , Okada Yukinori , Matsuda Koichi , Matsuo Keitaro , Kochi Yuta ,   Japanese Research Committee on Idiopathic Osteonecrosis of the Femoral Head, Kottyan Leah C. , Weirauch Matthew T. , Parameswaran Sreeja , Eswar Shruti , Salim Hanan , Chen Xiaoting , Yamamoto Kazuhiko , Harley John B. , Ohmura Koichiro , Kim Tae-Hwan , Yang Sen , Yamamoto Takuaki , Kim Bong-Jo , Shen Nan , Ikegawa Shiro , Lee Hye-Soon , Zhang Xuejun , Terao Chikashi , Cui Yong , Bae Sang-Cheol
Published: August 2020

Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci1-8. Nevertheless, these loci only partially explain SLE heritability and provide limited biological insight. We report the largest study of SLE in East Asians (13,377 cases and 194,993 controls), identifying 233 association signals within 113 (46 novel) genetic loci. We detect six new lead missense variants and prioritize ten most likely putative causal variants, one of which we demonstrate exhibits allele-specific regulatory effect on ACAP1 in vitro. We suggest 677 effector genes with potential for drug repurposing, and provide evidence that two distinct association signals at a single locus act on different genes (NCF2 and SMG7). We demonstrate that SLE-risk variants overlap with cell-specific active regulatory elements, notably EBNA2-mediated super-enhancers in Epstein-Barr Virus-transformed B cells, and implicate the role for non-immune cells in SLE biology. These findings shed light on genetic and biological understandings of SLE.
Evidence of SARS-CoV-2 transcriptional activity in cardiomyocytes of COVID-19 patients without clinical signs of cardiac involvement
Authors: Bulfamante Gaetano Pietro , Perrucci Gianluca Lorenzo , Falleni Monica , Sommariva Elena , Tosi Delfina , Martinelli Carla , Songia Paola , Poggio Paolo , Carugo Stefano , Pompilio Giulio
Published: August 2020

Background

Cardiovascular complication in patients affected by novel Coronavirus respiratory disease (COVID-19) are increasingly recognized. However, although a cardiac tropism of SARS-CoV-2 for inflammatory cells in autopsy heart samples of COVID-19 patients has been reported, the presence of the virus in cardiomyocytes has not been documented yet.

Methods

We investigated for SARS-CoV-2 presence in heart tissue autopsies of 6 consecutive COVID-19 patients deceased for respiratory failure showing no signs of cardiac involvement and with no history of heart disease. Cardiac autopsy samples were analysed by digital PCR, Western blot, immunohistochemistry, immunofluorescence, RNAScope, and transmission electron microscopy assays.

Results

The presence of SARS-CoV-2 into cardiomyocytes was invariably detected. A variable pattern of cardiomyocytes injury was observed, spanning from the absence of cell death and subcellular alterations hallmarks to the intracellular oedema and sarcomere ruptures. In addition, we found active viral transcription in cardiomyocytes, by detecting both sense and antisense SARS-CoV-2 spike RNA.

Conclusions

In this analysis of autopsy cases, the presence of SARS-CoV-2 into cardiomyocytes, determining variable patterns of intracellular involvement, has been documented. All these findings suggest the need of a cardiologic surveillance even in survived COVID-19 patients not displaying a cardiac phenotype, in order to monitor potential long-term cardiac sequelae.
Assessment of the risk of SARS-CoV-2 reinfection in an intense re-exposure setting
Authors: Abu Raddad Laith J. , Chemaitelly Hiam , Malek Joel A. , Ahmed Ayeda A. , Mohamoud Yasmin A. , Younuskunju Shameem , Ayoub Houssein H. , Kanaani Zaina Al , Khal Abdullatif Al , Kuwari Einas Al , Butt Adeel A. , Coyle Peter , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul Rahim Hanan F. , Yassine Hadi M. , Al Kuwari Mohamed G. , Romaihi Hamad Eid Al , Al Thani Sheikh Mohammad , Bertollini Roberto
Published: August 2020

Background

Reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is debated. We assessed risk and incidence rate of documented SARS-CoV-2 reinfection in a large cohort of laboratory-confirmed cases in Qatar.

Methods

All SARS-CoV-2 laboratory-confirmed cases with at least one PCR positive swab that is ≥45 days after a first-positive swab were individually investigated for evidence of reinfection, and classified as showing strong, good, some, or weak/no evidence for reinfection. Viral genome sequencing of the paired first-positive and reinfection viral specimens was conducted to confirm reinfection. Risk and incidence rate of reinfection were estimated.

Results

Out of 133,266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least one subsequent positive swab ≥45 days after the first-positive swab. Of these, 54 cases (22.2%) had strong or good evidence for reinfection. Median time between first and reinfection swab was 64.5 days (range: 45-129). Twenty-three of the 54 cases (42.6%) were diagnosed at a health facility suggesting presence of symptoms, while 31 (57.4%) were identified incidentally through random testing campaigns/surveys or contact tracing. Only one person was hospitalized at time of reinfection, but still with mild infection. No deaths were recorded. Viral genome sequencing confirmed four out of 12 cases with available genetic evidence. Risk of reinfection was estimated at 0.01% (95% CI: 0.01-0.02%) and incidence rate of reinfection was estimated at 0.36 (95% CI: 0.28-0.47) per 10,000 person-weeks.

Conclusions

SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of a strong protective immunity against reinfection that lasts for at least a few months post primary infection.