bluuebunny/crossref_metadata_2025 huggingface dataset:
Viscossuplementation for the treatment of osteoarthritis of the knee
Authors: Ferreira de Andrade Carlos Augusto , Genov Isabel Ruguê , Pereira Sara Regina Neto , Barreto Joao Mauricio , Ramos Max Rogério Freitas , da Silva Eduardo Costa Freitas , de Oliveira Liszt Palmeira
Published: September 2020

Background:

Knee osteoarthritis (KOA) is a common chronic disease with worldwide prevalence of 10% to 79%, with costs ranging from $560 to $635 billion for year in United States of America. The main guidelines recommend interventions with undesirable adverse events (AE) or highly dependent on the patient's persistence. Thus, intra-articular (IA) therapies appear to be attractive in patients with KOA, as well as a valid therapy by maximizing effects locally in the joint and limiting systemic AE. Presently, the main available IA therapies are corticosteroids and hyaluronic acid.

As several meta-analyses about the efficacy of intra-articular hyaluronic acid (IAHA) for treatment of KOA with discordant results were published, we decided to conduct an umbrella review to summarize this efficacy

Methods:

We will search MEDLINE/PubMed, EMBASE, Cochrane Library, and Virtual Health Library (BVS) from inception to February 2020 for systematic reviews with meta-analyses of randomized clinical trials that investigate IAHA for therapy of KOA. Grey literature will be searched in Opengray platform, Research Gate, and Google Scholar. The reference lists of eligible studies will be screened. The search will be performed without language restriction.

We will include any type of IAHA as experimental intervention and different types of oral or intra-articular placebo or medications as controls. The primary outcome will be measures of efficacy as the Western Ontario and McMaster Universities Osteoarthritis Index.

A synthesis of the evidence will be conducted and data will be presented in tables.

Two reviewers will independently appraise the quality of included meta-analyses using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and will classify the included systematic reviews into high, moderate, low, or critically low levels of confidence.

Results:

The results of this study will be published in a peer-reviewed journal.

Ethics and dissemination:

No ethical approval is required since this study data is based on published literature.

Protocol registration number:

PROSPERO CRD42019120269 (https://www.crd.york.ac.uk/PROSPERO/#joinuppage).
Usefulness of computed tomography venography in gynecologic cancer patients with lower extremity edema
Authors: Kim Won Jun , Kim JaYoung , Kang Minsoo , Park Dae Hwan , Jeon Jae Yong
Published: September 2020

Lower extremity (LEx) edema is a common complication in gynecologic cancer patients. There are 2 main causes of edema in these patients such as deep vein thrombosis (DVT) and lymphedema. Early diagnosis and treatment of DVT are certainly important, but it is often difficult to evaluate proximal DVT by using ultrasound. The aim of this study is to demonstrate the usefulness of computed tomography venography of the lower extremity (CTV LEx) for the diagnosis of the DVT and investigate predictive factor of DVT in gynecologic cancer patients with LEx edema.

The medical records of 415 gynecologic cancer patients who were referred to the department of rehabilitation medicine with LEx edema were retrospectively reviewed in this case-controlled study. We categorized CTV LEx findings as follows: DVT proximal to the inguinal ligament (inferior vena cava or iliac vein thrombosis) and DVT distal to the inguinal ligament (femoral, popliteal, or calf vein thrombosis). We also evaluated patient characteristics including d-dimer level. We analyzed the correlation of each factor with DVT frequency and used receiver operating characteristic curve analysis to determine the appropriate d-dimer threshold.

Sixty-six patients were diagnosed with DVT; of them, 35 (53%) had DVT proximal to the inguinal ligament. Twenty-two patients were diagnosed with pulmonary embolism, of whom 15 had proximal DVT. Patients with proximal DVT tended to have pulmonary embolism (P < .001). Distal organ metastasis (odds ratio [OR], 2.88; P = .002) and a high D-dimer level (OR, 1.13; P = .001) were correlated with DVT.

CTV LEx is a useful diagnostic tool for gynecologic cancer patients with LEx edema, particularly high-risk patients, that should be performed at the initial evaluation.
Wandering spleen with splenic torsion in a toddler
Authors: Wang Zhijun , Zhao Qiang , Huang Yuanyuan , Mo Zhanhao , Tian Zhisen , Yang Fan , Wang Yuanyi , Yao Liyu
Published: September 2020

Rationale:

Wandering spleen (WS) is a rare clinical entity characterized by splenic hypermobility caused by absent or abnormal laxity of the suspensory ligaments, which fix the spleen in its normal position. Due to abnormal attachment, the spleen is predisposed to torsion and a series of complications. Pediatric WS is mostly reported in children aged <10 years, especially among infants aged <1 year; it is uncommon among toddlers between 1 and 3 years. To the authors’ knowledge, only seven cases of WS have been described previously. Herein, we present the case of a 3-year-old toddler with WS and splenic torsion.

Patient concerns:

A 3-year-old boy was presented to the pediatric emergency room with a 2-day history of abdominal pain and vomiting. The ultrasonographic examination revealed a mass in the left upper abdomen cavity and absence of spleen in its normal position. Computed tomography showed an enlarged displaced spleen occupying the left abdomen cavity with an elongated splenic vascular pedicle (whirl sign), suggesting splenic torsion.

Diagnoses:

The patient was diagnosed that had WS and splenomegaly, with or without complications due to splenic torsion.

Interventions:

The patient underwent emergency laparotomy and splenectomy due to nonviability after detorsion.

Outcomes:

The postoperative course was uneventful, and the patient was discharged on the 7th day postoperatively without complications. The patient had favorable outcome over a 1-year follow-up.

Lessons:

Herein, we reported the case of a toddler with WS with splenic torsion. Moreover, after reviewing relevant studies in literature, we presented our findings on the diagnosis and treatment of toddlers with WS. Toddlers with WS are characterized by acute abdominal pain, unclear history description, examination restrictions, and high rates of life-threatening complications. High level of suspicion, careful physical examination, detailed history collection, and objective investigation are crucial in the management of toddlers with WS.
Long-term effects of phacoemulsification and intraocular lens implantation in a patient with pathologic myopia and extremely long axial length
Authors: Yang Yu , Chen Hao , An Jingqi , Fan Wei
Published: September 2020

Rationale:

To report a rare case of phacoemulsification cataract surgery and intraocular lens implantation that improved visual acuity and capsular stability in a patient with pathologic myopia and axial length >38 mm.

Patient concerns:

A 51-year-old Chinese man with high myopia since childhood who had lost sight in his left eye at the age of 25 due to retinal detachment. He was referred for ophthalmological assessment due to decreased vision in the right eye, in which the best-corrected visual acuity at distance was hand motion.

Diagnoses:

The patient was diagnosed with cataract, high myopia, subluxated lens, and loose zonules in the right eye. The left eyeball showed atrophy.

Interventions:

The patient underwent uneventful phacoemulsification. An intraocular lens (Sensar AR40M) and capsular tension ring were implanted within the capsular bag. After surgery, the patient was given eye drops containing tobramycin and dexamethasone eye drops for 1 month and eye drops containing 0.1% sodium diclofenac for 2 months.

Outcomes:

There were no postoperative complications. During 1-year follow-up, uncorrected visual acuity was 20/80 and the manifest refraction was −2.50DS/−1.00DC∗80, with corrected distance visual acuity of 20/60. Cataract surgery maintained adequate vision for daily living.

Lessons:

Implantation of specific lens and capsular tension ring as well as prolonged use of non-steroidal anti-inflammatory drugs may help prevent capsular contraction and posterior capsule opacification in patients with pathologic myopia and extremely long axial length.
The eighth version of American Joint Committee on Cancer nodal classification for high grade pancreatic neuroendocrine tumor should be generalized for the whole population with this disease
Authors: Li Mu-xing , Wang Hang-yan , Yuan Chun-hui , Ma Chao-lai , Jiang Bin , Li Lei , Zhang Li , Zhao Hong , Cai Jian-qiang , Xiu Dian-rong
Published: September 2020

Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.

We identified pNETs patients from SEER database (2004–2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.

A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ2) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all).

The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.
Diagnostic value of the enhancement intensity and enhancement pattern of CESM to benign and malignant breast lesions
Authors: Chi Xiaoxiao , Zhang Lei , Xing Dong , Gong Peiyou , Chen Qianqian , Lv Yongbin
Published: September 2020

This study aimed to improve the diagnostic accuracy of breast diseases by combining breast imaging–reporting and data system (BI–RADS) with the enhancement intensity and pattern of contrast-enhanced spectral mammography (CESM) (this combination of BI–RADS and CESM was designated as BaC).

BI–RADS was used to evaluate low-energy CESM images. Spearman nonparametric correlation analysis was performed to analyze the correlation between the enhancement intensity of CESM subtraction images and the pathological results. Odds ratio (OR) values were calculated to determine whether the enhancement pattern of CESM subtraction images is a risk factor for benign and malignant lesions. The diagnostic efficacies of BI–RADS, CESM, and BaC scores for benign and malignant breast diseases were analyzed using the receiver operating characteristic (ROC) curve.

Lesions with a high enhancement intensity were more likely to be malignant than those with low enhancement intensity. Lesions with heterogeneous enhancement tended to be malignant, whereas those with homogeneous enhancement tended to be benign. No significant correlation was observed between ring enhancement and the benignity or malignancy of lesions. The area under the ROC curve of BaC was higher than that of BI–RADS or CESM, and the difference was statistically significant.

The diagnostic efficacy of BI–RADS combined with CESM enhancement was superior to that of either method alone.
Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion
Authors: Kwon Jaewoo , Shin Sang Hyun , Yoo Daegwang , Hong Sarang , Lee Jong Woo , Youn Woo Young , Hwang Kyungyeon , Lee Seung Jae , Park Guisuk , Park Yejong , Lee Woohyung , Song Ki Byung , Lee Jae Hoon , Hwang Dae Wook , Kim Song Cheol
Published: September 2020

Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy.

This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12–26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (≥grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P = .06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P = .01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P 
= .04).

Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.
Deletion of b1/b3 shows risk for expanse of Yq microdeletion in male offspring
Authors: Liu Xiangyin , Zhang Hongguo , Yu Yang , Fei Jia , Jiang Yuting , Liu Ruizhi , Wang Ruixue , Zhang Guirong
Published: September 2020

Rationale:

This study aimed to report 1 family case with novel Y chromosome structural variations by an established next-generation sequencing (NGS) method using unique STSs.

Patient concerns:

The case studied was from a family with a father and son (the proband). G-band staining was used for karyotype analysis. Y chromosome microdeletions were detected by sequence-tagged site (STS)-PCR analysis and a new NGS screening strategy.

Diagnoses:

Semen analysis showed that the proband was azoospermic. The patient had an abnormal karyotype (45,X[48%]/46,XY[52%]). His father exhibited a normal karyotype. STS-PCR analysis showed that the proband had a deletion of the AZFb+c region, and his father had no deletion of STS markers examined. The sequencing method revealed that the patient had DNA sequence deletions from nt 20099846 to nt 28365090 (8.3 Mb), including the region from yel4 to the Yq terminal, and his father exhibited a deletion of b1/b3 and duplication of gr/gr.

Interventions:

The proband was advised to undergo genetic counseling, and consider the use of sperm from a sperm bank or adoption to become a father.

Outcomes:

The proband was azoospermic. AZFc partial deletions may produce a potential risk for large AZFb+c deletions or abnormal karyotypes causing spermatogenic failure in men.

Lessons:

The NGS method can be considered a clinical diagnostic tool to detect Y chromosome microdeletions. The partial AZFc deletions and/or duplications can be a risk of extensive deletions in offspring.
Clinical study on a skin stretching technique with adjustable external fixators to treat skin defects
Authors: Wang Gaofei , Zhang Xiuli , Zhang Zhufeng , Wei Zhuang
Published: September 2020

The aim of this study was to determine the effectiveness of a skin stretching technique with adjustable external fixators in treating skin defects.

Eighteen patients treated with a skin-stretching technique with adjustable external fixators for skin defects from April 2017 to October 2019 were included. Visual Analogue Scale (VAS) scores were collected during therapy. The skin defects gradually became smaller until they were completely resolved according to the blood flow of the affected limb and wound skin (the color, temperature, elasticity, and capillary response). The defect sizes ranged from 4 cm × 2 cm to 20 cm × 6 cm.

The 18 adjustable external fixators were dismantled in 2 to 9 days (mean, 4.05 days) after the operation, and the defects were completely closed and the sutures were removed after 2 to 3 weeks. The average VAS score was 5.97. The follow-up period was 4 to 12 months (mean, 6.3 months); 17 patients healed well with linear small scar, and no infections or patients of necrosis were observed. Sensory recovery was assessed using the Medical Research Council scale, and all the sensation scores were S3+. Eight patients were healed after the first stage. Nine patients were closed totally while small sinus or skin defect were observed after sutures were removed; 3 patients were healed after the second debridement, and 6 patients finally healed after the dressings were changed. Patellar osteomyelitis recurred in 1 patient who was transferred to the Orthopedic Department for further treatment, and a flap graft procedure was performed.

The operation was simple and obviously reduced the course of the disease, the costs, and the damage to the donor site, and it is also significantly superior to skin graft or flap transplantation procedures in terms of the resulting skin sensation, color, texture, elasticity, and appearance.
Fascia iliaca compartment block for analgesia in total hip replacement
Authors: Song Jiannan , Qiao Yan , Zhou Qi , Zhang Xizhe
Published: September 2020

Background:

Pain management after the total joint arthroplasty is still challenging, but worthy of attention, because good pain management can improve the outcomes of patient. It is still controversial whether fascia iliaca compartment block (FICB) can effectively decrease the opioid consumption and pain after total hip replacement (THR) owing to the number of published investigations is small. The purpose of this present study is to assess the efficacy and safety of FICB for postoperative analgesia after THR.

Methods:

This is a single center, placebo-controlled randomized trial which is performed in accordance with the SPIRIT Checklist for randomized studies. It was authorized via the Chifeng Municipal Hospital institutional review committee (H2020-19-8). 100 patients undergoing THR will be included in this study. Patients are randomly divided into 2 groups: FICB group or Non-FICB group, FICB with 5mgmL–1 of epinephrine and 40 mL of ropivacaine 0.2%. Primary outcomes are pain score at different time point. Visual analog scale is used to assess the pain (10: the maximum possible pain and 0: absent pain). The secondary outcomes are the postoperative complications, length of hospital stay and total consumption of opioid. All the needed analyses are implemented through utilizing SPSS for Windows Version 15.0.

Results:

Figure 1 will show the primary and secondary outcomes.

Conclusion:

This trial can provide an evidence for the use of FICB for analgesia after THR.
A comparison of pregnancy rate between natural cycle and hormone replacement cycle in patients who underwent frozen embryo transfer using 2 consecutive hormone replacement regiments
Authors: Pang Conghui , Guo Lin , Bi Yanyan , Wang Kehua , Lian Fang , Wu Zhijuan , Xu Xiaoyan , Sun Zhengao
Published: September 2020

For frozen embryo transplantation patients who failed to use hormone replacement cycle (HRC) transplantation for 2 consecutive times, the third time of transplantation was divided into 2 groups: HRC and natural cycle (NC), and the pregnancy rate of the 2 groups, especially the clinical pregnancy rate, was compared.

Retrospective study of 174 patients in the reproductive medicine center of an affiliated hospital of Shandong University of Traditional Chinese Medicine between January 2015 and September 2018.

The 174 patients were all infertile with regular menstruation. They had undergone 2 consecutive failed cycles of endometrial preparation with hormone replacement therapy and prepare for the third frozen embryo transplantation.

A third cycle of treatment was planned using either NC or HRC for endometrial preparation. All the embryos were obtained during the same oocyte retrieval cycle. Patients were divided into groups based on the method of endometrial preparation: 98 were classified as NC and 76 as HRC.

The pregnancy outcomes for the 2 groups were compared. Confounding factors that may affect clinical pregnancy rates were analyzed.

We found that on the day of endometrial transformation, estrogen levels and endometrial thickness in the NC group were significantly higher than those in the HRC group. There were no significant differences in the rates of biochemical pregnancy, clinical pregnancy, cumulative pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy, or live birth between the 2 groups. It is concluded by binary regression analysis that the different endometrial preparation protocol have no significant effect on the CPR.

NC is as effective as HRC after 2 previous cycles of HRC. Because this was a retrospective study design, selection bias is possible, although the baseline characteristics of the 2 groups of patients were matched.
Superb microvascular imaging evaluating joint lesion scores in rheumatoid arthritis compared with power Doppler imaging
Authors: Lin MingXin , Wang Cong
Published: September 2020

Background:

To compare superb microvascular imaging with power Doppler imaging for evaluating joint lesion scores in rheumatoid arthritis based on high quality clinical cohort or case control studies.

Methods:

We searched Medline (via PubMed), Web of Science, Cochrane Library, Embase, and Chinese Biomedical Literature Database without restrictions of language and publication status. Two investigators will identify relevant trials, extract data, and appraise risk of bias in each eligible trial. Data will be pooled by either a fixed-effects model or a random-effects model according to the results of heterogeneity identification. The primary outcomes include a semi-quantitative scoring system, through which synovial vascularity intensity was evaluated by means of both power Doppler imaging (PDI) and superb microvascular imaging (SMI). This study will only include high quality clinical cohort or case control studies. Statistical analyses were conducted by STATA version 15.1 software.

Results:

This meta-analysis included 11 studies. A total of 4342 joints were assessed through both SMI and PDI. The pooled summary odds ratio was 2.12 (95% confidence interval = 1.80–2.51) with statistical significance (z = 8.82, P < .01). In subgroup analyses, the results revealed also that SMI exhibited more sensitive performance in different subgroups. We found no evidence for publication bias (t = 0.55, P = .598).

Conclusion:

Our meta-analysis indicates that SMI ultrasound is more sensitive than conventional PDI in detecting synovitis in RA patients.

INPLASY Registration Number:

INPLASY202060089.
Intradermal acupuncture for primary dysmenorrhea
Authors: Xu Donghan , Wang Lizhen , Deng Lu , Luo Yehao , Wei Yan , Yan Peiyu
Published: September 2020

Background:

Primary dysmenorrhea (PD) is one of the common gynecological diseases, the incidence of PD is on the rise and young women are more likely to have it, which seriously affects women's physical, mental health and work life. Intradermal acupuncture is effective in treating PD. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on intradermal acupuncture and provide effective evidence for further research.

Methods:

We will search the following electronic databases from their inception to July 2020: Electronic database includes PubMed, Embase, Cochrane Library, Chinese Biomedical Database WangFang, VIP medicine information, and CNKI (China National Knowledge Infrastructure). Primary outcomes: the overall effective rate, VAS score. Secondary outcomes: blood serum estradiol (E2), progesterone (P), prostaglandin F2α (PGF-2α), adverse events Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0.

Results:

The results of this study will systematically evaluate the effectiveness and safety of intradermal acupuncture in the treatment of primary dysmenorrhea.

Conclusion:

The systematic review of this study will summarize the currently published evidence of intradermal acupuncture therapy for primary dysmenorrhea to further guide its promotion and application.
The effect of Baduanjin exercise on the quality of life in patients recovering from COVID-19
Authors: Ma Qian , Yang Zhihua , Zhu Feng , Chen Haojia , Yang Haolin , Wang Shuping
Published: September 2020

Background:

Since the outbreak of COVID-19, the number of COVID-19 patients has been on the rise. With the improvement of diagnosis and treatment level in various countries, more and more patients have recovered. Baduanjin exercise is a traditional Chinese health care method with a long history, easy-to-learn, and remarkable effect. It is not subject to the constraints of the field and can be practiced at any time. It can be used as an alternative therapy for COVID-19 rehabilitation patients. At present, there are no relevant articles for systematic review.

Methods:

We will retrieve a randomized controlled trial of Baduanjin exercise for COVID-19 from the beginning to July 2020. The following databases are areas of concern: Published randomized Cochrane Central Register of Controlled Trials (Central), PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan-fang Database-controlled trials in Chinese and English related to Baduanjin exercise and COVID-19 were included. The main result was the effect of Baduanjin exercise on the quality of life in patients recovering from COVID-19. Secondary results to accompany symptoms (such as muscle pain, cough, sputum, runny nose, sore throat, chest tightness, shortness of breath, difficulty breathing, fatigue, headache, nausea, vomiting, anorexia, diarrhea), disappearance rate, 2 consecutive (not on the same day) COVID-19 negative rate of nucleic acid test results, the quality of life improved, improve CT images, the average hospitalization time, severe form of common clinical cure rate and mortality.

Results:

The results of this study will provide researchers in the field of COVID-19 with a current synthesis of high-quality evidence.

Conclusion:

The conclusion of this study will provide evidence for judging whether Baduanjin exercise is an effective intervention for the quality of life of rehabilitative patients.

PROSPERO registration number:

CRD42020199443
Predictive Prenatal Diagnosis for Infantile‐onset Inflammatory Bowel Disease Because of Interleukin‐10 Signalling Defects
Authors: Ye Ziqing , Hu Wenhui , Wu Bingbing , Zhang Yueping , Lei Caixia , Williams Isabelle , Shouval Dror S. , Kanegane Hirokazu , Kim Kyung Mo , de Ridder Lissy , Shah Neil , Ling Galina , Yerushalmi Baruch , Kotlarz Daniel , Snapper Scott , Horn Ruth , Klein Christoph , Muise Aleixo M. , Huang Ying , Uhlig Holm H.
Published: September 2020

Objectives:

Advances in genetic technologies provide opportunities for patient care and ethical challenges. Clinical care of patients with rare Mendelian disorders is often at the forefront of those developments. Whereas in classical polygenic inflammatory bowel disease (IBD), the predictive value of genetic variants is very low, predictive prenatal genetic diagnosis can inform families at high risk of severe genetic disorders. Patients with IL‐10 signalling defects because of pathogenic variants in IL10RA, Il10RB, and IL10 develop severe infantile onset inflammatory bowel disease that is completely penetrant and has a high morbidity and substantial mortality despite treatment.

Methods:

We performed a survey among tertiary specialist paediatric centers of 10 countries on the utilization of predictive prenatal genetic diagnosis in IL‐10 signalling defects. We retrospectively report prenatal genetics in a series of 8 families.

Results:

International variation in legislation, guidelines, expert opinion, as well as cultural and religious background of families and clinicians results in variable utilization of preimplantation and prenatal genetic testing for IL‐10 signalling defects. Eleven referrals for prenatal diagnosis for IL‐10 signalling defects were identified across 4 countries. We report on 8 families who underwent prenatal preimplantation monogenic testing after in vitro fertilization (n = 2) and/or by amniocentesis/chorion villus sampling (n = 6). A genetic diagnosis was established in 1 foetus and excluded in 7 foetuses (all IL10RA variants).

Conclusions:

Prenatal genetic testing for IL10R‐defects is feasible, yet the legal and ethical considerations are complex and controversial. In some countries, predictive genetics for IL‐10‐related signalling defects is entering clinical practice.
Illness Stigma, Worry, Intrusiveness, and Depressive Symptoms in Youth With Inflammatory Bowel Disease
Authors: Roberts Caroline M. , Baudino Marissa N. , Gamwell Kaitlyn L. , Edwards Clayton S. , Traino Katherine A. , Tung Jeanne , Grunow John E. , Jacobs Noel J. , Mullins Larry L. , Chaney John M.
Published: September 2020

Background:

Youth who experience IBD‐associated stigma may manifest increased worry about aversive symptoms that can intrude on their participation in routine activities (eg, school, social events), potentially resulting in limited opportunities for reinforcement and increased depressive symptoms. The present study examined an IBD stigma → IBD worry → illness intrusiveness → depressive symptoms serial mediation model, in which stigma was hypothesized to confer an indirect effect on youth depressive symptoms through the serial effects of stigma on IBD worry and illness intrusiveness.

Methods:

Youth with IBD (N = 90) between the ages of 10 and 18 years were recruited from a pediatric gastroenterology clinic and completed measures of IBD stigma, IBD worry, illness intrusiveness, and depressive symptoms.

Results:

In addition to several independent direct effects among the modeled variables, results revealed a significant IBD stigma → IBD worry → illness intrusiveness → depressive symptoms serial mediation path (effect = 0.63, 95% CI = 0.22 to 1.20), controlling for youth sex and IBD severity.

Conclusions:

The experience of IBD‐related stigma may prompt increased worry about IBD symptoms, independent of the influence of disease activity. Further, heightened worry appears to amplify youths’ experience of IBD‐imposed limitations on routine and rewarding activities, increasing their risk for experiencing depressive symptoms. Our findings highlight the importance of regular screening for depressive symptoms, as well as the identification of potential risk factors associated with emotional adjustment difficulties. Stigma‐specific treatment modules could be integrated within existing cognitive‐behavioral approaches for reducing worry and depressive symptoms in youth with IBD.
Giant Rhinophyma
Authors: Wang Yan , Allen Philip W.
Published: September 2020

A 42-year-old woman presented with a clinically obvious giant rhinophyma. The protocol of the unit handling the case mandated that all lesions amenable to biopsy should have a core biopsy before any definitive surgery, but the unnecessary biopsy was not representative and suggested an incorrect diagnosis of perifollicular fibroma. The lesion was excised. The sections showed dilated hair follicle pores on the skin surface, squamous lined hair follicles plugged with keratin, prominent sebaceous glands, perifollicular inflammation without granulomas, intradermal budding of hair follicle basal cells, and extensive hypocellular, mildly edematous fibrous tissue with slightly dilated, thin-walled vessels and a few chronic inflammatory cells. These fully representative sections confirmed the diagnosis of giant rhinophyma, suggesting that preoperative core biopsies of this condition are unnecessary and may be misleading.
Mucous Gland Adenoma: The Spectrum of Growth Patterns and the Diagnostic Challenges
Authors: Zaleski Michael P. , Kalhor Neda , Moran Cesar A.
Published: September 2020

Mucous gland adenomas represent a small percentage of primary lung neoplasms. The accurate diagnosis of these benign tumors can be challenging not only on resected specimens but also more challenging in small bronchoscopic biopsies. If to that problem we add the issue that these tumors may also exist in the periphery of the lung, then it is easy to conclude that there is much difficulty in properly diagnosing these tumors with a core needle biopsy. Furthermore, there is little knowledge on the immunohistochemical properties and radiologic features of these tumors. Therefore, pathologists need to be aware of the spectrum of histopathologic features in these tumors and place them in perspective regarding the proper radiologic and immunohistochemical correlations. Needless to say, mucous gland adenomas exhibit a gamut of histopathologic features that can be easily confused with other more common tumor of the lung. Therefore, awareness of such features become essential in a benign tumor that is essentially diagnosed on morphologic grounds.
Clinical Course of COVID-19 Infection in Patients Urgently Operated of Cardiac Surgical Procedures
Authors: Garatti Andrea , Castelvecchio Serenella , Daprati Andrea , Molfetta Raffaella , Volpe Marianna , De Vincentiis Carlo , Parolari Alessandro , Menicanti Lorenzo
Published: September 2020

Objective:

The aim of this study was to describe the clinical course of a consecutive series of patients operated of urgent cardiac surgery during COVID-19 outbreak.

Background:

In Italy, COVID outbreak has mostly occurred in the metropolitan area of Milan, and in the surrounding region of Lombardy, and previously “conventional” hospitals were converted into COVID spokes to increase ICU beds availability, and to allow only urgent CS procedures.

Methods:

Among urgent CS patients (left main stenosis with unstable angina, acute endocarditis, valvular regurgitation with impending heart failure), 10 patients (mean age = 57 ± 9 years), despite a negative admission triage, developed COVID-pneumonia postoperatively, at a median of 7 days after CS.

Results:

Patients showed typical lymphopenia, higher prothrombotic profile, and higher markers of inflammation (ferritin and interleukin-6 values). At the zenith of pulmonary distress, patients presented with severe hypoxia (median PaO2/FIO2 ratio = 116), requiring advanced noninvasive ventilation (Venturi mask and continuous positive airway pressure) in the majority of cases. All patients were treated with hydroxychloroquine, azithromycin, and low-molecular-weight heparin at anticoagulant dose. Overall in-hospital mortality was 10% (1/10), peaking 25% in patients who developed COVID pneumonia immediately after CS. The remaining patients, with late infection, were all discharged home without oxygen support, at a median of 25 days after symptom onset.

Conclusions:

As postoperative mortality in case of COVID pneumonia is not negligible, meticulous rules (precise triage, safe hospital path, high level of protection for health-care teams, prompt diagnosis of suspicious symptoms) should be strictly followed in patients undergoing CS during COVID pandemic. The role of therapies alternative to CS should be further assessed.
Proposal of 'Candidatus Frankia alpina', the uncultured symbiont of Alnus alnobetula and A. incana that forms spore-containing nitrogen-fixing root nodules
Authors: Pozzi Adrien C. Meynier , Herrera-Belaroussi Aude , Schwob Guillaume , Bautista-Guerrero Hector H. , Bethencourt Lorine , Fournier Pascale , Dubost Audrey , Abrouk Danis , Normand Philippe , Fernandez Maria P.
Published: September 2020

The members of the genusFrankiaare, with a few exceptions, a group of nitrogen-fixing symbiotic actinobacteria that nodulate mostly woody dicotyledonous plants belonging to three orders, eight families and 23 genera of pioneer dicots. These bacteria have been characterized phylogenetically and grouped into four molecular clusters. One of the clusters, cluster 1 contains strains that induce nodules onAlnusspp. (Betulaceae),Myricaspp.,Morellaspp. andComptoniaspp. (Myricaceae) that have global distributions. Some of these strains produce not only hyphae and vesicles, as other cluster 1 strains do, but also numerous sporangia in their host symbiotic tissues, hence their phenotype being described as spore-positive (Sp+). While Sp+ strains have resisted repeated attempts at cultivation, their genomes have recently been characterized and found to be different from those of all described species, being markedly smaller than their phylogenetic neighbours. We thus hereby propose to create a 'CandidatusFrankia alpina' species for some strains present in nodules ofAlnus alnobetulaandA. incanathat grow in alpine environments at high altitudes or in subarctic environments at high latitudes.
Agrobacterium cavarae sp. nov., isolated from maize (Zea mays L.) roots
Authors: Flores-Félix José David , Menéndez Esther , Ramírez-Bahena Martha Helena , Peix Alvaro , García-Fraile Paula , Velázquez Encarna
Published: September 2020

A bacterial strain designated as RZME10T was isolated from a Zea mays L. root collected in Spain. Results of analysis of the 16S rRNA gene sequence showed that this strain belongs to the genus

Agrobacterium

with

Agrobacterium larrymoorei

ATCC 51759T being the most closely related species with 99.9 % sequence similarity. The similarity values of the rpoB, recA, gyrB, atpD and glnII genes between strain RZME10T and

A. larrymoorei

ATCC 51759T were 93.5, 90.0, 88.7, 87.9 and 90.1 %, respectively. The estimated average nucleotide identity using blast and digital DNA–DNA hybridization values between these two strains were 80.4 and 30.2 %, respectively. The major fatty acids of strain RZME10T are those from summed feature 8 (C18 : 1 ω6c/C18 : 1 ω7c) and C16 : 0. Pathogenicity tests on tomato and carrot roots showed that strain RZME10T was not able to induce plant tumours. Based on the results of genomic, chemotaxonomic and phenotypic analyses, we propose that strain RZME10T represents a novel species named Agrobacterium cavarae sp. nov. (type strain RZME10T=CECT 9795T=LMG 31257T).
Heterogeneity and Superspreading Effect on Herd Immunity
Authors: Oz Yaron , Rubinstein Ittai , Safra Muli
Published: September 2020

We model and calculate the fraction of infected population necessary for herd immunity to occur, taking into account the heterogeneity in infectiousness and susceptibility, as well as the correlation between the two parameters. We show that these cause the reproduction number to decrease with progression, and consequently have a drastic effect on the estimate of the necessary percentage of the population that has to contract the disease for herd immunity to be reached. We discuss the implications to COVID-19 and other pandemics.
Comparing synthetic refocusing to deconvolution for the extraction of neuronal calcium transients from light-fields
Authors: Howe Carmel L. , Quicke Peter , Song Pingfan , Jadan Herman Verinaz , Dragotti Pier Luigi , Foust Amanda J.
Published: September 2020

Significance

Light-field microscopy (LFM) enables fast, light-efficient, volumetric imaging of neuronal activity with calcium indicators. Calcium transients differ in temporal signal-to-noise ratio (tSNR) and spatial confinement when extracted from volumes reconstructed by different algorithms.

Aim

We evaluated the capabilities and limitations of two light-field reconstruction algorithms for calcium fluorescence imaging.

Approach

We acquired light-field image series from neurons either bulk-labeled or filled intracellularly with the red-emitting calcium dye CaSiR-1 in acute mouse brain slices. We compared the tSNR and spatial confinement of calcium signals extracted from volumes reconstructed with synthetic refocusing and Richardson-Lucy 3D deconvolution with and without total variation regularization.

Results

Both synthetic refocusing and Richardson-Lucy deconvolution resolved calcium signals from single cells and neuronal dendrites in three dimensions. Increasing deconvolution iteration number improved spatial confinement but reduced tSNR compared to synthetic refocusing. Volumetric light-field imaging did not decrease calcium signal tSNR compared to interleaved, widefield image series acquired in matched planes.

Conclusions

LFM enables high-volume rate, volumetric imaging of calcium transients in single cells (bulk-labeled), somata and dendrites (intracellular loaded). The trade-offs identified for tSNR, spatial confinement, and computational cost indicate which of synthetic refocusing or deconvolution can better realize the scientific requirements of future LFM calcium imaging applications.
pmparser and PMDB: resources for large-scale, open studies of the biomedical literature
Authors: Schoenbachler Joshua L. , Hughey Jacob J.
Published: September 2020

PubMed is an invaluable resource for the biomedical community. Although PubMed is freely available, the existing API is not designed for large-scale analyses and the XML structure of the underlying data is inconvenient for complex queries. We developed an R package called pmparser to convert the data in PubMed to a relational database. Our implementation of the database, called PMDB, currently contains data on over 31 million PubMed Identifiers (PMIDs) and is updated regularly. Together, pmparser and PMDB can enable large-scale, reproducible, and transparent analyses of the biomedical literature. pmparser is licensed under GPL-2 and available athttps://pmparser.hugheylab.org. PMDB is stored in PostgreSQL and compressed dumps are available on Zenodo (https://doi.org/10.5281/zenodo.4008109).
Investigating motor preparatory processes and conscious volition using machine learning
Authors: Hall Siobhan , van den Heever Dawie , Vinding Mikkel C. , Morris Linzette
Published: September 2020

Background

Conscious volition is a broad term and is difficult to reduce to a single empirical paradigm. It encompasses many areas of cognition, including decision-making and empirical studies can be done on these components. This work follows on the seminal work of Libetet al. (1983) which focused on brain activity preceding motor activity and conscious awareness of the intention to move. Previous results have subsequently faced criticism, particularly methods used to average out EEG data over all the trials and the readiness potential not being present on an individual trial basis. This following study aims to address these criticisms.

Objectives

To use machine learning to investigate brain activity preceding left/right hand movements with relation to conscious intent and motor action.

Methodology

The data collection involved the recreation of the Libet experiment, with electroencephalography (EEG) data being collected. An addition made in this study was the choice between “left” and “right” while observing the Libet clock to subjectively mark the moment of conscious awareness. Twenty-one participants were included (four females, all right-handed). A deep (machine) learning model known as a convolutional neural network (CNN) was used for the EEG data analysis.

Results

Subjectively reported conscious intent preceded the action by 108 ms. The CNN model was able to predict the decision “left” or “right” as early as 4.45 seconds before the action with a test accuracy of 98%.

Conclusion

This study has shown motor preparatory processes start up to 4.45 seconds before conscious awareness of a decision to move.
Diversity, phylogeny and DNA barcoding of brachyuran crabs in artificially created mangrove environments
Authors: Manikantan Ganesh , PrasannaKumar Chinnamani , Vijaylaxmi J. , Pugazhvendan S. R. , Prasanthi Narra
Published: September 2020

Globally, at the rate of 1-2 percent per annum, mangrove coverings are disappearing and 35 percent have been lost in the last 20 years due to changes in climate and human activities. No mangrove-associated crabs were found when the mangroves were artificially transplanted 25 years ago in the Vellar estuary. This mangrove ecosystem was sampled for brachyuran biodiversity estimation, species abundance, composition and evaluation of the effectiveness of DNA barcoding in brachyuran crabs species identification. A total of 2844 crabs were collected, representing 35 species within 8 families belonging to 20 genera. Four brachyuran crab species, that is,Uca lactae, U. Triangularis, Selatium brockii, andNeosarmatium asiaticumaccount for >70% of the total abundance. An approximate 87.5% of crab species estimated to occur by various species estimator were recovered in the present study. BetweenUca lacteaandU. triangularis, the maximum association index value was observed (97.7%). Cluster analysis grouped the sampled stations according to the types of mangrove species, clearly influencing the structure and composition of the brachyuran crabs. In general, vegetative cover composed of multiple species of mangroves is preferred for the abundance of all collected crabs species, and particularlyNeosarmatium asiaticum. Analysis of DNA barcoding indicates that 40% of the brachyuran species gathered in this sample were first barcoded. The advent of new high-throughput sequencing technologies will change biomonitoring applications and surveys drastically in the near future, making reference datasets like ours relevant.
Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases
Authors: Weeks Elle M. , Ulirsch Jacob C. , Cheng Nathan Y. , Trippe Brian L. , Fine Rebecca S. , Miao Jenkai , Patwardhan Tejal A. , Kanai Masahiro , Nasser Joseph , Fulco Charles P. , Tashman Katherine C. , Aguet Francois , Li Taibo , Ordovas-Montanes Jose , Smillie Christopher S. , Biton Moshe , Shalek Alex K. , Ananthakrishnan Ashwin N. , Xavier Ramnik J. , Regev Aviv , Gupta Rajat M. , Lage Kasper , Ardlie Kristin G. , Hirschhorn Joel N. , Lander Eric S. , Engreitz Jesse M. , Finucane Hilary K.
Published: September 2020

Genome-wide association studies (GWAS) are a valuable tool for understanding the biology of complex traits, but the associations found rarely point directly to causal genes. Here, we introduce a new method to identify the causal genes by integrating GWAS summary statistics with gene expression, biological pathway, and predicted protein-protein interaction data. We further propose an approach that effectively leverages both polygenic and locus-specific genetic signals by combining results across multiple gene prioritization methods, increasing confidence in prioritized genes. Using a large set of gold standard genes to evaluate our approach, we prioritize 8,402 unique gene-trait pairs with greater than 75% estimated precision across 113 complex traits and diseases, including known genes such as SORT1 for LDL cholesterol, SMIM1 for red blood cell count, and DRD2 for schizophrenia, as well as novel genes such as TTC39B for cholelithiasis. Our results demonstrate that a polygenic approach is a powerful tool for gene prioritization and, in combination with locus-specific signal, improves upon existing methods.