bluuebunny/crossref_metadata_2025 huggingface dataset:
The epidemiological and clinical characteristics of the hospital-acquired influenza infections
Authors: Li Yi , Wang Lan-Lan , Xie Li-Li , Hou Wei-Lian , Liu Xiao-Yi , Yin Shi
Published: March 2021

Background:

The hospital-acquired influenza (HAI) were usually contributed to severe outcomes among the inpatients. Here, we performed a meta-analysis to summarize and quantify the epidemiological and clinical characteristics of HAI.

Methods:

We performed a literature search thorough PubMed, Web of Science, Cochrane Library, Embase, Scopus and China National Knowledge Infrastructure (CNKI), and Wanfang databases for observational studies. Random/fix-effects models were used to obtain pooled proportion, odds ratio (OR), and weighted mean difference (WMD).

Results:

A total of 14 studies involving 1483 HAI and 71849 non-hospital-acquired influenza infections (NHAI) cases were included.The proportion of the HAI among the influenza cases was 11.38% (95% confidence interval [CI]: 5.19%–19.55%) and it was increased after 2012 (6.15% vs 12.72%). The HAI cases were significantly older (WMD = 9.51, 95% CI: 0.04–18.98) and the patients with chronic medical diseases were at increased risk of HAI (OR = 1.85, 95% CI: 1.57–2.19). Among them, metabolic disorders (OR = 8.10, 95% CI: 2.46–26.64) ranked the highest danger, followed by malignancy (OR = 3.18, 95% CI: 2.12–4.76), any chronic diseases (OR = 2.81, 95% CI: 1.08–9.31), immunosuppression (OR = 2.13, 95% CI: 1.25–3.64), renal diseases (OR = 1.72, 95% CI:1.40–2.10), heart diseases (OR = 1.52, 95% CI: 1.03–1.44), and diabetes (OR = 1.22, 95% CI: 1.03–1.44). The HAI cases were more likely to experience longer hospital stay (WMD = 10.23, 95% CI: 4.60–15.85) and longer intensive care unit (ICU) stay (WMD = 2.99, 95% CI: 1.50–4.48). In the outcomes within 30 days, those population was still more likely to receive hospitalization (OR = 6.55, 95% CI: 5.19–8.27), death in hospital (OR = 1.99, 95% CI: 1.65–2.40) but less likely to discharged (OR = 0.20, 95% CI: 0.16–0.24).

Conclusion:

The proportion of the HAI among the influenza cases was relatively high. Reinforcement of the surveillance systems and vaccination of the high-risk patients and their contacts are necessary for the HAI control.
Pharmacists’ perception of educational material to improve patient safety
Authors: Said André , Freudewald Leonard , Parrau Natalie , Ganso Matthias , Schulz Martin
Published: March 2021

Educational material (EM) addresses particular safety information of medicinal products to healthcare professionals and patients. Since 2016, German national competent authorities label approved EM with a Blue Hand symbol. However, data is scarce regarding its usability as a safety communication tool in pharmacies to improve patient safety. The purpose of this study is to investigate for the first time pharmacists’ awareness and perception of EM in the setting of community and hospital pharmacies in Germany.

The Drug Commission of German Pharmacists surveyed its nationwide network of 677 community and 51 hospital reference pharmacies, to investigate their awareness and perception of EM. The survey was conducted between January 16 and February 10, 2020 using SurveyMonkey. Data were analyzed using Microsoft Excel.

A total of 373 community and 32 hospital pharmacists participated; response rates were 55.1% and 62.8%, respectively. Overall, 320 (85.8%) community and all hospital pharmacists confirmed awareness of EM. Community and hospital pharmacists fully (n = 172, 46.9% and n = 9, 28.1%) or rather (n = 109, 29.7% and n = 10, 31.3%) agreed that EM for healthcare professionals is suitable to reduce risks of medicinal products. Moreover, 237 (64.7%) community and 17 (53.1%) hospital pharmacists confirmed to inform patients or care facilities about EM. Asking pharmacists on their personal perception of EM, the refinement of readability and accessibility was indicated.

Pharmacists confirm awareness of EM and its suitability as a safety communication tool. However, from a pharmacists’ perspective, the applicability and readability of EM still needs further adjustment to improve patient safety.
Accuracy of noninvasive continuous arterial pressure monitoring using ClearSight during one-lung ventilation
Authors: Lee Sang-Wook , Lee Sangho , Kim Hyungtae , Kim Yun-Jong , Kim Mihyeon , Choi Jeong-Hyun
Published: March 2021

Noninvasive continuous arterial pressure monitoring may be clinically useful in patients who require continuous blood pressure monitoring in situations where arterial catheter placement is limited. Many previous studies on the accuracy of the noninvasive continuous blood pressure monitoring method reported various results. However, there is no research on the effectiveness of noninvasive arterial pressure monitoring during one-lung ventilation. The purpose of this study was to compare arterial blood pressure obtained through invasive method and noninvasive method by using ClearSight during one-lung ventilation.

In this retrospective observational study, a total of 26 patients undergoing one-lung ventilation for thoracic surgery at a single institution between March and July 2019 were recruited. All patients in this study were cannulated on their radial artery to measure continuously invasive blood pressures and applied ClearSight on the ipsilateral side of the cannulated arm. We compared and analyzed the agreement and trendability of blood pressure recorded with invasive and noninvasive methods during one-lung ventilation.

Blood pressure and pulse rate showed a narrower limit of agreement with a percentage error value of around 30%. In addition, the tracking ability of each measurement could be determined by the concordance rate, all of which were below acceptable limits (92%).

In noninvasive arterial blood pressure monitoring using ClearSight, mean blood pressure and pulse rate show acceptable agreement with the invasive method.
A novel PMP22 insertion mutation causing Charcot–Marie–Tooth disease type 3
Authors: Han Liang , Huang Yanjing , Nie Yuan , Li Jing , Chen Gang , Tu Shenghao , Shen Pan , Chen Chao
Published: March 2021

Rationale:

Charcot–Marie–Tooth disease (CMT) is a group of hereditary neuropathies with clinical features of muscle atrophy, sensory loss, and foot deformities. CMT is related to a number of genes, such as peripheral myelin protein 22 gene (PMP22). Missense mutations, small deletion mutations, and duplications of PMP22 are common in CMT patients, but few insertion mutation cases of PMP22 have been reported.

Patient concerns:

A 26-year-old male patient with the complaint of general weakness, peroneal atrophy, and deformities in the extremities visited our hospital. The patient was born with bilateral thumbs and feet dystonia. Additionally, delayed feet arch development and delayed walking was observed when he was a child.

Diagnosis:

Using whole-exome sequencing and electrophysiological test, we identified a novel insertion mutation of PMP22 (NM_153322, c.54_55insGTGCTG, p.(L19delinsVLL)) in a 26-year-old male patient with peroneal atrophy and nerve conduction was not elicited in electromyography (EMG) study. The Protein Variation Effect Analyzer (PROVEAN) program analysis predicted that the variant is likely to be “deleterious.” SWISS-MODEL program predicted that alpha helix in original location was disrupted by inserted 6 bases, which may account for the occurrence of CMT3.

Interventions:

The patient received symptomatic and supportive treatments, and routine rehabilitation exercises during hospitalization.

Outcomes:

The condition of the patient was improved, but the disease could not be cured. At 1- and 3-months follow-up, manifestations of the patient were unchanged, and he could take care of himself.

Lessons:

Our findings link a novel PMP22 mutation with a clinical diagnosis of CMT3. The link between gene variation and CMT phenotype may help to reveal the structure and function of PMP22 protein and the pathogenesis of CMT. This study adds further support to the heterogeneity of PMP22 related CMT and provides solid functional evidence for the pathogenicity of the p.(L19delinsVLL) PMP22 variant. Moreover, with the development of high-throughput sequencing technology, the combination of next-generation sequencing (NGS) and conventional Sanger sequencing is becoming one of the comprehensive, inexpensive, and convenient tools for genetic diagnosis of CMT.
Intraspinal clear cell meningioma without dural attachment
Authors: Zhang Xiaolei , Zhang Peihai , Wang James Jin , Dong Sheng , Wu Youtu , Zhang Huifang , Wang Guihuai
Published: March 2021

Rationale:

Clear cell meningioma (CCM) is one of the rarest but most aggressive forms of meningioma, with a tendency to occur at a high recurrence rate. Intraspinal CCM, especially the nondura-based type, is even rarer than the intracranial CCM.

Patient concerns:

We report a case of a 45-year-old woman who presented with a 1-month history of episodic pain in the lower back and in both thighs in the front side. Femoral nerve stretch tests were positive on both sides. Magnetic resonance imaging (MRI) demonstrated an intradural tumor at the L3 level, which was isointense on T1- and T2-weighted images (WI) and homogeneously enhanced on gadolinium-contrast T1 WI.

Diagnoses:

The space-occupying lesion was pathologically confirmed as CCM.

Interventions:

During surgery, we found that the tumor adhered to a nerve root, without dural attachment. The nerve root was partially removed to achieve complete resection.

Outcomes:

The pain disappeared after the operation. The 1 year follow-up MRI revealed no evidence of tumor recurrence or metastasis.

Lessons:

Nondura-based intraspinal CCM is easier to completely remove, and such complete removal should be achieved during the first operation. Although the recurrence rate of this particular type of meningioma appears to be lower than that of other types, close clinical and radiological follow-up is necessary.
Psychodynamic day treatment program for borderline personality disorder: factors that predict outcome and dropout
Authors: Pec Ondrej , Bob Petr , Pec Jan , Ludvikova Irena
Published: March 2021

The objective of this study was to ascertain changes in symptoms of patients with borderline personality disorder undergoing psychodynamic day treatment with a duration of 9 months and the factors that predict clinical outcome or dropouts from the program.

In an observational study, demographic characteristics (age, number of psychiatric hospitalizations, number of suicide attempts, current involvement in work or study activities), day doses of antipsychotic and antidepressant medication, psychiatric symptoms, and social functioning (Health of the Nation Outcome Scales), and symptoms of dissociation (Dissociative Experiences Scale) were assessed in patients at the beginning of treatment (N = 105). Further, psychiatric symptoms and social functioning were assessed at 3 stages: beginning of the program, end of the program, and 1-year follow-up. To study the differences between baseline values and values at the end of the treatment and follow-up values, the Wilcoxon signed-rank test was used. To discover baseline factors related to the effect of the treatment, Spearman correlation coefficients were calculated. To evaluate the differences between patients who completed the program (N = 67) and patients who dropped out (N = 38), differences in baseline factors between both groups were compared, using the Mann–Whitney test for independent samples.

Improvement in symptoms (Health of the Nation Outcome Scales – version for external evaluators) at the end of the therapy (N = 67, P < .001) and at the 1-year follow-up (N = 46, P < .001) was found. Experience of an intimate relationship was positively related to clinical improvement at follow-up examinations (P < .001). Predictors of dropout included a higher number of psychiatric hospitalizations (P = .004), suicide attempts (P = .004), more severe pretreatment symptoms (P = .002), and symptoms of dissociation (P = .046).

The results indicate that a psychodynamic day treatment is feasible for the treatment of less clinically disturbed patients with a history of intimate relationships. Patients with a higher number of previous psychiatric hospitalizations, more suicide attempts in the past, more severe pretreatment symptoms, and symptoms of dissociation are more likely not to complete the program.
Correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood
Authors: Wang Na , Eerdun Gaowa , Dong Yan , Hao Ling , Li Tiezhi
Published: March 2021

The present study was conducted with an attempt to explore the correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.

The levels of umbilical cord blood resistin, adiponectin, insulin, growth hormone, leptin, thyrotropin, thyroid hormone (T3, T4), lgM, lgA, lgG, CD4, and CD8 were measured in 180 full-term newborns delivered in hospital from October 2018 to November 2019. The delivery mode, weight, height, and gender at birth were recorded.

The levels of resistin, insulin, and growth hormone in umbilical cord blood of newborns delivered vaginally were significantly higher than those born by cesarean section (P < .05), while the levels of adiponectin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable between the 2 groups (P > .05). The levels of resistin, adiponectin, insulin, growth hormone, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 in cord blood of male and female newborns were comparable (P > .05). The newborns with birth weight ≥ 3501 g reported comparable results in the levels of resistin and growth hormone compared with those with birth weight of 3000 to 3500 g (P > .05), but were significantly higher than those with birth weight ≤ 2999 g (P < 0.05). In addition, the levels of adiponectin, insulin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable among the 3 groups (P > .05). Based on Pearson correlation analysis, neonatal umbilical cord blood resistin was positively correlated with adiponectin, leptin, growth hormone, T3, and T4 (r = 0.281, 0.287, 0.321, 0.276, 0.269, P < .05). However, there was no significant correlation between neonatal umbilical cord blood resistin and insulin, TST, lgM, lgA, lgG, CD4, and CD8.

The level of serum resistin in neonatal umbilical cord blood was associated with the delivery mode and birth weight, and positively correlated with adiponectin, leptin, growth hormone, T3, and T4. However, no correlation was observed between serum resistin in neonatal umbilical cord blood and insulin, TST, lgM, lgA, lgG, CD4, and CD8.
Effectiveness of Tong-Xie-Yao-Fang combined with Si-Ni-San for irritable bowel syndrome
Authors: Jiang Jiawang , Chen Yun , Hu Ziyi , Li Huaiyu , Ye Jing , Yu Zhiying , Tang Haiyi
Published: March 2021

Background:

Irritable bowel syndrome (IBS) has a high morbidity rate worldwide, but there are no effective treatment measures, which seriously affect people's lives. Previous clinical studies on Tong-Xie-Yao-Fang (TXYF) combined with Si-Ni-San (SNS) in the treatment of IBS have been increasing, but there is no systematic evaluation. This study aims to systematically study the effectiveness of TXYF combined with SNS in the treatment of IBS.

Methods:

The PubMed, EMBASE, Science Network, Cochrane Library, Chinese Biomedical Literature, Wanfang Chinese Digital Journal and Conference Database, China National Knowledge Infrastructure Database and VIP China Science and Technology Journal Database (VIP) will be used Search related literature, and the search time is from the date of establishment to February 2021. The National Institutes of Health clinical registry Clinical Trials, International Clinical Trials Registry Platform and the Chinese clinical trial registration platform will be searched to find ongoing or unpublished trials. After screening the literature according to the criteria, two researchers independently extracted data according to a predetermined table. The primary outcome is total effective rate. The RevMan 5.3.5 software will be used for statistical analysis. Finally, the recommendation, evaluation, development and evaluation system will be used to evaluate the quality evidence for each result.

Results:

This study will provide the latest evidence of efficacy for the TXYF combined with SNS for IBS.

Conclusion:

The effectiveness of TXYF combined with SNS for IBS will be evaluated.

Unique INPLASY number:

INPLASY202120075.
Open and/or laparoscopic one-stage resections of primary colorectal cancer and synchronous liver metastases
Authors: Nozawa Hiroaki , Ishizawa Takeaki , Yasunaga Hideo , Ishii Hiroaki , Sonoda Hirofumi , Emoto Shigenobu , Murono Koji , Sasaki Kazuhito , Kawai Kazushige , Akamatsu Nobuhisa , Kaneko Junichi , Arita Junichi , Hasegawa Kiyoshi , Ishihara Soichiro
Published: March 2021

One-stage resections of primary colorectal cancer and liver metastases have been reported to be feasible and safe. Minimally invasive approaches have become more common for both colorectal and hepatic surgeries. This study aimed to investigate outcomes of these combined surgical procedures among different approaches.

We retrospectively analyzed patients diagnosed as having primary colorectal cancer with synchronous liver metastases and who underwent 1-stage primary resection and hepatectomy with curative intent in our hospital. According to the surgical approach for the primary tumor and hepatic lesions, namely open laparotomy (Op) or laparoscopic approach (Lap), patients were classified into Op-Op, Lap-Op (laparoscopic colorectal resection plus open hepatectomy), and Lap-Lap groups, respectively. Clinicopathological factors were reviewed, and short- and long-term outcomes were compared among the groups.

The Op-Op, Lap-Op, and Lap-Lap groups comprised 36, 18, and 17 patients, respectively. The superior/posterior hepatic segments were more frequently resected via an open approach. There was no laparoscopic major hepatectomy. The median volume of intraoperative blood loss was smaller in the Lap-Lap and Lap-Op groups (290 and 270 mL) than in the Op-Op group (575 mL, P = .008). The hospital stay after surgery was shorter in the Lap-Lap and Lap-Op groups (median: 17 days and 15 days, vs 19 days for the Op-Op group, P = .033). The postoperative complication rates and survivals were similar among the groups.

Application of laparoscopy to 1-stage resections of primary colorectal cancer and liver metastases may offer advantages of enhanced recovery from surgical treatment, given appropriate patient selection.
Clinical predictors of readmission after surgery for Hirschsprung disease
Authors: Min Jie , Cai Peng , Wu Bin , Gu Zhicheng , Huang Shungen , Wang Jian
Published: March 2021

The reasons for readmission of children with Hirschsprung disease (HD) are multiple. The study aims to predict the relevant factors for the readmission of children with HD by collecting and analyzing the relevant data of the child's admission to the hospital at the time of surgery.

A retrospective review was performed including all patients with surgical treatment of HD at our institution between the years of 2011 to 2020. Univariate and multivariate Logistic regression analysis were performed to obtain the independent risk factor for this study. The receiver operating characteristic curve (ROC) were used to assess the performance of derived models.

A total of 162 patients were identified. The average presurgery weights were 6.93 ± 1.78 kg in the readmission group and 8.38 ± 3.17 kg in the non-readmission group. Six children were classified as a low-weight in the readmission group, and 11 children classified as low-weight in the non-readmission group. The length of the intestinal tube after resection was 25.25 ± 15.21 cm in the readmission group, and 16.23 ± 4.10 cm in the non-readmission group. The ROC for the prediction model of readmission after HD surgery (AUC = 0.811).

In children undergoing the HD surgery, we showed preoperative low body weight and long intra-operative bowel resection significantly increase the probability of readmission due to complications.
Ecological, convergent, and discriminative validities of the cognitive abilities screening instrument in people with dementia
Authors: Jian Zi-Hua , Li Chih-Ping , Chiu En-Chi
Published: March 2021

Background:

The Cognitive Abilities Screening Instrument (CASI) assesses global cognitive function in people with dementia with 9 domains (i.e., long-term memory, short-term memory, concentration, orientation, attention, abstraction and judgment, language abilities, visual construction, and category fluency). However, the ecological, convergent, and discriminant validities of the CASI have not yet been examined.

Purpose:

This study designed to investigate these 3 validities of the CASI in people with dementia.

Methods:

Fifty-eight participants underwent assessments with the CASI, 3 functional measures, and 3 cognitive measures. Pearson's r was used to estimate correlations among the CASI and 3 functional measures for examining ecological validity. We computed correlations (r) among the CASI and 3 functional measures for examining convergent validity. An independent t-test was applied to compare the levels of disability, and ceiling/floor effects were analyzed for examining discriminative validity.

Results:

The CASI total score and domains had moderate to high correlations with 3 functional measures (r = 0.42–0.80), except in 2 CASI domains (i.e., attention and language). The CASI total score and domains showed moderate to high correlations with 3 cognitive measures (r = 0.45–0.93). The t-test results revealed significant differences (P < .05) in the CASI total score and other domains except for the short-term memory domains. Four domains of the CASI showed noticeable ceiling effects (22.4–39.7%).

Conclusions:

The CASI has adequate ecological validity, good convergent validity, and acceptable discriminative validity in people with dementia. The 5 domains with nonsignificant differences or ceiling effects should only be used with caution to distinguish people with dementia.
A short-term exercise program in patients with multiple sclerosis: is body mass index important?
Authors: Aykin Yiğman Zeynep , Karaahmet Özgür Zeliha , Avşar Ertürk Fatma , Yiğman Fatih
Published: March 2021

Obesity is a health problem that can exacerbate the symptoms of multiple sclerosis (MS). In the current study, we aimed to investigate the effectiveness of a short-term exercise program on fatigue, depression, anxiety, and walking performance in normal-weight and overweight patients with MS (PwMS). Sixty-two PwMS were divided into groups according to their BMI (BMI normal/BMI high). Also, they were all included in the exercise program. The participants took a moderate-intensity walking program 5 days a week for 4 weeks, including 30 min between 5 min of warm-up and 5 min of cooling periods. Also, patients underwent breathing, posture, flexibility, and stretching exercises for 4 weeks. Fatigue, depression, anxiety, 6-minute walking test (6MWT), and BMI were measured before and after the 4 weeks. After the exercise program, there were statistically significant improvements in fatigue, depression, anxiety, and the 6MWT. However, no relation could be detected between the examined variables and BMI. All patients participated effectively in the exercise program, regardless of BMI. The results obtained from this study support that a short-term exercise program is an effective therapeutic intervention, unrelated to BMI, in improving fatigue, depression, anxiety, and walking performance in PwMS.
Recommendations and Guidance on Nutritional Supplementation in the Liver Transplant Setting
Authors: Campos-Varela Isabel , Gómez-Gavara Concepción , Augustin Salvador
Published: March 2021

Malnutrition is a frequent complication in patients with cirrhosis and liver transplant (LT) candidates. It is highly related to sarcopenia, and their implications in morbidity and mortality go beyond the waiting list period throughout the post-LT. However, there are no specific interventions defined by guidelines regarding the kind or the timing of the nutritional intervention to improve LT outcomes. Results from studies developed in the LT setting and evaluating their impact on the LT candidates or recipients are discussed in this review, and new research lines are presented.
Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C
Authors: Tse Chung Sang , Yang Ju Dong , Mousa Omar Y. , Nelson Kevin M. , Pungpapong Surakit , Keaveny Andrew , Aqel Bashar A. , Vargas Hugo , Dickson Rolland C. , Watt Kymberly , Gores Gregory J. , Roberts Lewis R. , Leise Michael D.
Published: March 2021

Background:

Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC).

Methods:

We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models.

Results:

A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time.

Conclusions:

Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.
Impact of New UNOS Allocation Criteria on Heart Transplant Practices and Outcomes
Authors: Liu Jason , Yang Bin Q. , Itoh Akinobu , Masood Mohammed Faraz , Hartupee Justin C. , Schilling Joel D.
Published: March 2021

Background.

In October 2018, a new heart allocation policy was implemented with intent of prioritizing the sickest patients and decreasing waitlist time. We examined the effects of the new policy on transplant practices and outcomes 1 year before and 1 year after the change.

Methods.

Transplant recipients from October 2017 to September 2019 at our institution were identified and divided into 2 cohorts, a preallocation and postallocation criteria change. Patient demographics, clinical data, and bridging strategy were assessed. Early outcomes including ischemic time, severe primary graft dysfunction, need for renal replacement therapy, and duration of hospital stay were investigated.

Results.

In the 12 months before the change, 38 patients were transplanted as compared to 33 patients in the 12 months after the change. The average wait-time to transplant decreased after the allocation change (49 versus 313 d, P = 0.02). Patients were more likely to be bridged with an intra-aortic balloon pump (45% versus 3%) and less likely to be supported with a durable left ventricular assist device (LVAD) after the change (24% versus 82%). There was an increase in total ischemic time after the change (177 versus 117 min, P ≤ 0.01). There were no significant differences in other early posttransplant outcomes.

Conclusions.

Implementation of the new allocation system for heart transplantation resulted in dramatic changes in the bridging strategy utilized at our institution. Temporary mechanical support usage increased following the change and the number of recipients supported with durable LVADs decreased. Early posttransplant outcomes appear similar.
Destination Transplant: Protocol for a Parallel-group Randomized Trial of an Educational Intervention to Increase Kidney Transplant Among Black People on the Transplant Waiting List
Authors: Weng Francis L. , Davis LaShara A. , Ohman-Strickland Pamela A. , Waterman Amy D.
Published: March 2021

Background.

For most patients with kidney failure, living donor kidney transplant (LDKT) is their best treatment option. Compared with White people, Black people are more likely to have kidney failure but less likely to receive LDKTs. In this study, the investigators will test an educational intervention, Destination Transplant, designed to reduce this disparity, among Black people already listed for kidney transplant.

Methods.

The investigators will conduct a parallel group, 2-arm randomized clinical trial among 500 Black kidney transplant candidates. The main objective of this study is to test an educational and behavioral intervention that is designed to increase receipt of LDKT among transplant candidates (persons active on the deceased donor kidney transplant waiting list) who are Black. Candidates on the kidney transplant waiting list will be randomly assigned to 1 of 2 conditions: (1) a control group that will receive Usual Care, or (2) an Intervention group that will receive Destination Transplant, a 9-month intervention that includes an in-person group-based education session, postcards at monthly intervals, and a follow-up phone call from a transplant educator. At baseline and during 18 months of follow-up, demographic and clinical variables will be collected, as well as variables such as transplant derailers (factors that might be sources of delay, difficulty, or challenge to pursuing transplant), transplant knowledge, and health literacy, small steps taken to pursue LDKT, readiness for LDKT, decisional balance and self-efficacy LDKT, decisional conflict, family support, availability of potential living donors, and general health status.

Conclusions.

This educational intervention aims to increase both readiness to pursue LDKT and actual receipt of LDKTs among Black and African American patients who are already on the kidney transplant waiting list. The aim of the intervention is to reduce racial disparities in access to LDKT.
Paradoxical effect of statin medication on depressive disorder in first-ever ischemic stroke patients: possible antidepressant-like effect prestroke and the opposite in continuous medication poststroke
Authors: Li Yanbo , Guo Yijia , Zhou Muke , Ma Mengmeng , Fang Jinghuan , He Li
Published: March 2021

Poststroke depression (PSD) is the most frequent complication after stroke. Statin is a widely used prophylactic for stroke. However, some researchers reported that poststroke statin may lead to a depressive change in stroke patients. We aimed to study the effect of different statin medication timing especially prestroke timing on PSD to adopt appropriate intervention around stroke. Patients with first-ever ischemic stroke were consecutively observed from January 2012 to June 2017. They were grouped by different initiation time of statin treatment. The follow-up endpoints were set to: (1) diagnosis of PSD within 1-year and (2) censor data. Cox regression model adjusted for confounding factors was performed. A total of 1571 patients were included in the analyses, among which 210 (13.4%) were comorbided with PSD, and the median time of the course was 30 (14–98) days. The patients who received both pre- and poststroke statin treatment had 1.99 times (P = 0.037) the hazard faced by patients who did not receive that medication. In contrast, sole statin pretreatment may have the tendency to reduce the risk of PSD. Our findings provide the primary results for the prestroke statin medication. The initiation timing of continuous regular statin treatment ahead of ischemic stroke could have a correlation with a higher risk of PSD.
Mucilaginibacter aquatilis sp. nov., Mucilaginibacter arboris sp. nov., and Mucilaginibacter ginkgonis sp. nov., novel bacteria isolated from freshwater and tree bark
Authors: Kang Heeyoung , Kim Haneul , Bae Seokhyeon , Joh Kiseong
Published: March 2021

Three Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacterial strains, designated as HME9299T, HMF7410T and HMF7856T, were isolated from freshwater and tree bark collected in Yong-in, Republic of Korea. Strains HME9299T, HMF7410T and HMF7856T exhibited the highest 16S rRNA gene sequence similarities of 97.2, 94.4 and 96.4 % to

Mucilaginibacter daejeonensis

Jip 10T,

Mucilaginibacter terrae

CCM 8645T and

Mucilaginibacter phyllosphaerae

PP-F2F-G21T, respectively. Among themselves, the values were 94.1–95.7 %. Phylogenetic analysis of the 16S rRNA gene sequences of the three isolates revealed that they belonged to the genus

Mucilaginibacter

within the family

Sphingobacteriaceae

. The predominant fatty acids of three strains were summed feature 3 (comprising C16 : 1
 ω7c and/or C16 : 1
 ω6c) and iso-C15 : 0. Strain HME9299T contained a relatively large amount of C16 : 1
 ω5c. The predominant respiratory quinone was menaquinone-7. The genome sizes of strains HME9299T, HMF7410T and HMF7856T were 4.33, 4.16 and 3.68 Mbp, respectively, and their DNA G+C contents were 41.6, 38.4 and 43.9 mol%, respectively. Based on the results of the phenotypic, genotypic, chemotaxonomic and phylogenetic investigation, three novel species, Mucilaginibacter aquatilis sp. nov, Mucilaginibacter arboris sp. nov. and Mucilaginibacter ginkgonis sp. nov., are proposed. The type strains are HME9299T (=KCTC 42122T=DSM 29146T), HMF7410T (=KCTC 62464T=NBRC 113227T) and HMF7856T (=KCTC 72782T=NBRC 114275T), respectively.
Differential gene expression by RNA-Seq in Sigma-2 Receptor/TMEM97 knockout cells reveals its role in complement activation and SARS-CoV-2 viral uptake
Authors: Riad Aladdin , Aubert Yann , Zeng Chenbo , Graham Thomas J. A. , Petersson E. James , Capell Brian C. , Mach Robert H.
Published: March 2021

Our lab has recently shown that the Sigma-2 Receptor/Transmembrane Protein 97 (sigma-2R/TMEM97) interacts with the low-density lipoprotein receptor (LDLR) and facilitates the enhanced uptake of various ligands including lipoproteins and intrinsically disordered proteins. TMEM97 has been recently been shown to interact with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins, highlighting its potential involvement with viral entry into the cell. We hypothesized that sigma-2R/TMEM97 may play a role in facilitating viral uptake, and with the regulation of inflammatory and thrombotic pathways that are involved with viral infection. In this study, we identified the top differentially expressed genes upon the knockout of sigma-2R/TMEM97, and analyzed the genes involved with the inflammatory and thrombotic cascades, effects that are observed in patients infected with SARS-CoV-2. We found that the ablation of sigma-2R/TMEM97 resulted in an increase in Complement Component 4 Binding Protein (C4BP) proteins, at both the translational and transcriptional levels. We also showed that sigma-2R/TMEM97 interacts with the cellular receptor for SARS-CoV-2, the human angiotensin-converting enzyme 2 (ACE2) receptor, forming a protein complex, and that disruption of this complex results in the inhibition of viral uptake. The results of this study suggest that sigma-2R/TMEM97 may be a novel therapeutic target to inhibit SARS-CoV-2 viral uptake, as well as to decrease inflammatory and thrombotic effects through the modulation of the complement cascade.
The virucidal effects of 405 nm visible light on SARS-CoV-2 and influenza A virus
Authors: Rathnasinghe Raveen , Jangra Sonia , Miorin Lisa , Schotsasert Michael , Yahnke Clifford , Garcίa-Sastre Adolfo
Published: March 2021

Germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit its use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) as well as the influenza A virus to 405nm, visible light in the absence of exogenous photosensitizers indicating a potential porphyrin-independent alternative mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are generally safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.
Understanding SARS-CoV-2 Infection and Dynamics with Long Term Wastewater based Epidemiological Surveillance
Authors: Tharak Athmakuri , Kopperi Harishankar , Hemalatha Manupati , Kiran Uday , Gokulan C. G. , Moharir Shivranjani , Mishra Rakesh K , Mohan S Venkata
Published: March 2021

Wastewater-based epidemiology (WBE) of SARS-CoV-2 emerged as an advantageous method to study the infection dynamics at substantial population level. A temporal glimpse at sewage viral genome helps as diagnostic tool to understand the viral spread at community level. In this study, for the long-term epidemiological surveillance, we monitored the SARS-CoV-2 genetic material in domestic sewage by adopting the longitudinal sampling to represent a selected community (∼1.8 lakhs population which occupies 1.79% of the total population of Hyderabad city) to understand the dynamics of infection. Dynamics and spread of COVID-19 outbreak within the selected community were achieved by studying the longitudinal sampling for a specific period of time. WBE also promotes clinical scrutiny along with disease detection and management, in contrast to an advance warning signal to anticipate outbreaks.
Novel MOG analogues to explore the MCT2 pharmacophore, α-ketoglutarate biology and cellular effects ofN-oxalylglycine
Authors: Fets Louise , Bevan Natalie , M. Nunes Patrícia , Campos Sebastien , dos Santos Mariana Silva , Sherriff Emma , MacRae James I. , House David , Anastasiou Dimitrios
Published: March 2021

α-ketoglutarate (αKG) is a central metabolic node with a broad influence on cellular physiology. The αKG analogueN-oxalylglycine (NOG) and its membrane-permeable pro-drug derivative dimethyl-oxalylglycine (DMOG) have been extensively used as tools to study prolyl hydroxylases (PHDs) and other αKG-dependent processes. In cell culture media, DMOG is rapidly converted to MOG, which enters cells through monocarboxylate transporter MCT2, leading to intracellular NOG concentrations that are sufficiently high to inhibit glutaminolysis enzymes and cause cytotoxicity. Therefore, the degree of (D)MOG instability together with MCT2 expression levels determine the intracellular targets NOG engages with and, ultimately, its effects on cell viability. Here we designed and characterised a series of MOG analogues with the aims of improving stability and exploring the functional requirements for interaction with MCT2, a relatively understudied member of the SLC16 family. We report MOG analogues that maintain ability to enter cells via MCT2, and identify compounds that do not inhibit glutaminolysis or cause cytotoxicity but can still inhibit PHDs. We use these analogues to show that glutaminolysis-induced activation of mTORC1 can be uncoupled from PHD activity. Therefore, these new compounds can help deconvolute cellular effects that result from the polypharmacological action of NOG.
Vtc5 is localized to the vacuole membrane by the conserved AP-3 complex to regulate polyphosphate synthesis in budding yeast
Authors: Bentley-DeSousa Amanda , Downey Michael
Published: March 2021

Polyphosphates (polyP) are energy-rich polymers of inorganic phosphates assembled into chains ranging from 3-1000s of residues in length. They are thought to exist in all cells on earth and play roles in an eclectic mix of functions ranging from phosphate homeostasis to cell signaling, infection control, and blood clotting. In the budding yeastSaccharomyces cerevisiae, polyP chains are synthesized by the vacuole-bound VTC complex, which synthesizes polyP while simultaneously translocating it into the vacuole lumen where it is stored at high concentrations. VTC’s activity is promoted by an accessory subunit called Vtc5. In this work, we find that the conserved AP-3 complex is required for proper Vtc5 localization to the vacuole membrane. In human cells, previous work has demonstrated that mutation of AP-3 subunits gives rise to Hermansky-Pudlak Syndrome, a rare disease with molecular phenotypes that include decreased polyP accumulation in platelet dense granules. In yeast AP-3 mutants, we find that Vtc5 is rerouted to the vacuole lumen by the ESCRT complex, where it is degraded by the vacuolar protease Pep4. Cells lacking functional AP-3 have decreased levels of polyP, demonstrating that membrane localization of Vtc5 is required for its VTC stimulatory activityin vivo. Our work provides insight into the molecular trafficking of a critical regulator of polyP metabolism in yeast. We speculate that AP-3 may also be responsible for the delivery of polyP regulatory proteins to platelet dense granules in higher eukaryotes.

HIGHLIGHTS

Vtc5 localization to the vacuole membrane depends on the AP-3 complex

The ESCRT pathway brings mislocalized Vtc5 to the vacuole lumen where it is degraded

Decreased polyP levels in AP-3 mutants are explained by Vtc5 mislocalization

Deletion ofDOA4restores wild-type localization of Vtc5 without restoring polyP levels
One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening
Authors: Urdaniz Irene Francino , Steiner Paul J. , Kirby Monica B. , Zhao Fangzhu , Haas Cyrus M. , Barman Shawn , Rhodes Emily R. , Peng Linghang , Sprenger Kayla G. , Jardine Joseph G. , Whitehead Timothy A.
Published: March 2021

The potential emergence of SARS-CoV-2 Spike (S) escape mutants is a threat to reduce the efficacy of existing vaccines and neutralizing antibody (nAb) therapies. An understanding of the antibody/S escape mutations landscape is urgently needed to preemptively address this threat. Here we describe a rapid method to identify escape mutants for nAbs targeting the S receptor binding site. We identified escape mutants for five nAbs, including three from the public germline class VH3-53 elicited by natural COVID-19 infection. Escape mutations predominantly mapped to the periphery of the ACE2 recognition site on the RBD with K417, D420, Y421, F486, and Q493 as notable hotspots. We provide libraries, methods, and software as an openly available community resource to accelerate new therapeutic strategies against SARS-CoV-2.

One Sentence Summary

We present a facile method to identify antibody escape mutants on SARS-CoV-2 S RBD.
An ecological basis for dual genetic code expansion in marine deltaproteobacteria
Authors: Kivenson Veronika , Paul Blair G. , Valentine David L.
Published: March 2021

Marine benthic environments may be shaped by anthropogenic and other localized events, leading to changes in microbial community composition evident decades after a disturbance. Marine sediments in particular harbor exceptional taxonomic diversity and can shed light on distinctive evolutionary strategies. Genetic code expansion may increase the structural and functional diversity of proteins in cells, by repurposing stop codons to encode noncanonical amino acids: pyrrolysine (Pyl) and selenocysteine (Sec). Here, we show that the genomes of abundant Deltaproteobacteria from the sediments of a deep-ocean chemical waste dump site, have undergone genetic code expansion. Pyl and Sec in these organisms appear to augment trimethylamine (TMA) and one-carbon metabolism, representing key drivers of their ecology. The inferred metabolism of these sulfate-reducing bacteria places them in competition with methylotrophic methanogens for TMA, a contention further supported by earlier isotope tracer studies and reanalysis of metatranscriptomic studies. A survey of genomic data further reveals a broad geographic distribution of a niche group of similarly specialized Deltaproteobacteria including at sulfidic sites in the Atlantic Ocean, Gulf of Mexico, Guayamas Basin, and North Sea, as well as in terrestrial and estuarine environments. These findings reveal an important biogeochemical role for specialized Deltaproteobacteria at the interface of the carbon, nitrogen and sulfur cycles, with their niche adaptation and ecological success seemingly enabled by genetic code expansion.
The PfAP2-HS transcription factor protects malaria parasites from febrile temperatures
Authors: Tintó-Font Elisabet , Michel-Todó Lucas , Russell Timothy J. , Casas-Vila Núria , Conway David J. , Bozdech Zbynek , Llinás Manuel , Cortés Alfred
Published: March 2021

Periodic fever is the most characteristic clinical feature of human malaria1-3, but how parasites survive febrile episodes is not known. WhilePlasmodiumspp. genomes encode a full complement of chaperones4, they lack an ortholog of the conserved transcription factor HSF1, which in most eukaryotes activates the expression of key chaperones upon heat shock (HS)5-8. Here we identified PfAP2-HS, a transcription factor of the ApiAP2 family9-11, as the key regulator of theP. falciparumprotective HS response. The PfAP2-HS-dependent HS response is largely restricted to rapid activation ofhsp70-1, the predominant direct target of PfAP2-HS, andhsp90. Deletion of PfAP2-HS dramatically reduced HS survival and also resulted in severe growth defects at 37°C, but not at 35°C, and increased sensitivity to imbalances in protein homeostasis (proteostasis) produced by artemisinin, the current frontline antimalarial drug12,13. These results demonstrate that PfAP2-HS contributes to general maintenance of proteostasis and drives a rapid chaperone-based protective response against febrile temperatures. While several ApiAP2 transcription factors regulate life cycle transitions in malaria parasites11,14,15, PfAP2-HS is the first identifiedPlasmodiumtranscription factor that controls a protective response to a within-host environmental challenge.