bluuebunny/crossref_metadata_2025 huggingface dataset:
The serum creatinine to cystatin C ratio predicts the risk of acute exacerbation of chronic obstructive pulmonary disease
Authors: He Liang , Li Yan , Gou Xijun , Lei Ling
Published: March 2023

The purpose of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) treatment is to minimize the negative impact of the current exacerbation and to prevent the development of subsequent events. Therefore, it is important to identify readily available serological indicators during hospital admission to assess the prognosis of patients with AECOPD. All patients hospitalized in a Department of Respiratory and Critical Care Medicine of tertiary care hospital between January 2021 and December 2021 for AECOPD were analyzed using univariate correlations and binary logistic regression analysis with 2 models for associations between demographic, clinical, and laboratory features and AECOPD risk. The ratio of creatinine to cystatin C (Cre/Cys C) ratio was significantly associated with age (r = −0.206, P = .000), weight (R = 0.331, P = .000), body mass index (BMI) (R = 0.133, P = .007), and forced vital capacity (FVC)% predicted (R = 0.130, P = .009). Multiple regression was performed to predict the Cre/Cys C ratio from age, weight, BMI, forced expiratory volume during 1 second/FVC ratio, and FVC% predicted FABP-4, with F (5, 405) = 24.571, P = .000, R2 = 0.233. The results showed that the most significant predictors of the Cre/Cys C ratio were age (P = .007), weight (P = .000), BMI (P = .000), and predicted forced expiratory volume during 1 second (P = .000). Multivariate analysis was performed to determine whether the Cre/Cys C ratio was a predictor of AECOPD risk. Model 1 showed that a low Cre/Cys C ratio was associated with an increased hospital length of stay (odds ratio: −0.114, 95% confidence interval: −0.061 to −0.005) and admission to the intensive care unit (odds ratio: 0.951, 95% confidence interval: 0.907–0.996). After adjustment for potential confounding factors, model 2 showed that a low Cre/Cys C ratio was not independently associated with AECOPD risk. The present study indicated that the Cre/Cys C ratio is an easy, cheap, repeatable, and promising tool that allows us to evaluate the risk of AECOPD using serum markers. A low Cre/Cys C ratio was associated with a prolonged hospital length of stay and admission to the intensive care unit in AECOPD patients. However, the associations were not independent.
Completeness and quality of information about death from COVID-19 in a Brazilian state: A descriptive population-based register study
Authors: Dell’Antonio Larissa Soares , Leite Franciéle Marabotti Costa , Dell’Antonio Cristiano Soares da Silva , Souza Camila Brandão de , Garbin Juliana Rodrigues Tovar , Santos Ana Paula Brioschi dos , Alves Micael Franco , Lopes-Júnior Luís Carlos
Published: March 2023

Health information is particularly essential in times of pandemics in which rapid response is crucial for political and stakeholder decision-making processes, and therefore the availability of data as well as its quality analysis are necessary. This study aimed to describe the completeness and quality of the e-Sistema Único de Saúde (SUS) Health Surveillance database (SUS Vigilância em Saúde) of the state of Espírito Santo, Brazil, from the notification of deaths from corana virus disease 2019 (COVID-19) from January 2020 to June 2021. A descriptive population-based register study was conducted from the analysis of the completeness of secondary data from the record of deaths from COVID-19, retrieved from the e-SUS Vigilância em Saúde (Health Surveillance) (VS) database of the state of Espírito Santo, Brazil, from January 2020 to June 2021. A total of 11,359 death records from COVID-19 via e-SUS VS in the state of Espírito Santo, Brazil, were evaluated. The score used to assess incompleteness was the 1 proposed by Romero and Cunha which classifies as excellent (when < 5%), good (between 5% and 10%), regular (between 10% and 20%), poor (between 20% and 50%), and very poor (when > 50%), according to the percentage of the absence of information. Descriptive statistical analyses were conducted in the Stata program, version 15.1. “Case identification” variables, and “condition” variables were classified as excellent completeness. Among the evolution variables, only “hospitalization” was classified as regular. Among the laboratory variables, only the polymerase chain reaction presented excellent completeness, while the “rapid test” and “serologies for immunoglobulin G, and immunoglobulin M” variables were classified as good completeness. It is concluded that most of the variables available in e-SUS VS of the state of Espírito Santo, Brazil, of notification of deaths from COVID-19 in 2020 presented excellent completeness, confirming the excellent quality of the state database.
Efficacy and safety of early chest tube removal after selective pulmonary resection with high-output drainage: A systematic review and meta-analysis
Authors: Zhu Junwei , Xia Xueyang , Li Rongyao , Song Weikang , Zhang Zhiqiang , Lu Huawei , Li Zhiwei , Guo Qingwei
Published: March 2023

Background:

There is controversy over the drainage threshold for removal of chest tubes in the absence of significant air leakage after selective pulmonary resection.

Methods:

A comprehensive search of online databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus, Ovid, Elsevier, Ebsco, and Wiley) and clinical trial registries (WHO-ICTRP and ClinicalTrials.gov) was performed to investigate the efficacy and safety of early chest tube removal with high-output drainage. Primary outcome (postoperative hospital day) and secondary outcomes (30-day complications, rate of thoracentesis, and chest tube placement) were extracted and synthesized. Subgroup analysis, meta-regression, and sensitivity analysis were used to explore the potential heterogeneity. Study quality was assessed with the Newcastle-Ottawa Scale, and evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment by the online GRADEpro Guideline Development Tool.

Results:

Six cohort studies with a total of 1262 patients were included in the final analysis. The postoperative hospital stay in the high-output group was significantly shorter than in the conventional treatment group (weighted mean difference: −1.34 [−2.34 to −0.34] day, P = .009). While there was no significant difference between 2 groups in 30-day complications (relative ratio [RR]: 0.92 [0.77–1.11], P = .38), the rate of thoracentesis (RR: 1.93 [0.63–5.88], P = .25) and the rate of chest tube placement (RR: 1.00 [0.37–2.70], P = .99). According to the sensitivity analysis, the relative impacts of the 2 groups had already stabilized. Subgroup analysis revealed that postoperative hospital stay was modified by Newcastle-Ottawa Scale score. The online GRADEpro Guideline Development Tool presented very low quality of evidence for the available data.

Conclusions:

This meta-analysis revealed that it is feasible and safe to remove a chest tube with high-output drainage after pulmonary resection for selected patients.
The ability of long non-coding RNA RP11-284N8.3 to predict the risk, the severity and 28-day mortality of adults with sepsis
Authors: Cheng Yanwei , Ding Ning , Cao Xue , Wang Jiaoyang , Zhang Jiange , Shi Xiaopeng , Xu Lijun , Qin Lijie
Published: March 2023

In a prior study, we identified a novel sepsis specific long noncoding RNAs (lncRNA) RP11-284N8.3, which may primarily participate in T cell activation and immune response during sepsis. However, the clinical significance of lncRNA RP11-284N8.3 in sepsis remains entirely unknown. This single-center prospective cohort study enrolled 147 adults with sepsis and 74 healthy controls (HCs) with matched age and sex between January 2021 and November 2022 at our hospital. Blood samples and clinical data were collected from HCs at enrollment and from adults with sepsis within 24 hours after admission. lncRNA RP11-284N8.3 expression was detected by RT-qPCR. The relative expression of lncRNA RP11-284N8.3 was significantly decreased in adults with sepsis compared to HCs (P < .0001), in adults with septic shock compared to adults without shock (P = .0012), and in 28-day deaths compared to 28-day survivors (P = .0006). receiver operating characteristic curves of lncRNA RP11-284N8.3 in predicting sepsis severity and 28-day mortality showed an area under the curve of 0.6570 (95% confidence interval [CI]: 0.5701–0.7440) and an area under the curve of 0.6765 (95% CI: 0.5809–0.7721), respectively. Multivariate logistic regression analysis revealed that lncRNA RP11-284N8.3 was an independent risk factor for 28-day mortality in adults with sepsis (odds ratio: 0.1057, 95% CI: 0.0115–0.7746, P = .0328). Low expression of lncRNA RP11-284N8.3 is correlated with increased risk, severity and 28-day mortality in adults with sepsis, and it may function as a potential biomarker to facilitate the diagnosis and management of sepsis.
A detective of intramural ectopic pregnancy: The use of pituitrin under hysteroscopy combined with laparoscopy
Authors: Guo Yanchao , Feng Tongfu , Du Xin
Published: March 2023

Rationale:

Intramural pregnancy is a rare ectopic pregnancy in which the gestational sac is implanted between the muscle walls. Due to the lack of specific clinical manifestations, it is easy to misdiagnose or miss them. If it is allowed to get worse, the uterus will burst, and there will be a lot of bleeding in the later stages, which could lead to the death of the patient.

Patient concerns:

The patient had no history of uterine surgery, embryo transplantation, or any other operations. She complained of having abdominal distention and swelling of the waist but no vaginal bleeding or lower abdomen discomfort.

Diagnoses:

According to her transvaginal ultrasonography, we highly suspected ectopic pregnancy. Hysteroscopy combined with laparoscopy is an effective treatment option that can prevent life-threatening problems. During the surgery, pituitrin helped find the gestational sac, and the pathology report confirmed that it was an intramural pregnancy.

Interventions:

Hysteroscopy combined with laparoscopy is an effective treatment option that can prevent life-threatening problems. During the surgery, we used pituitrin to help find the gestational sac. The use of pituitrin can minimize bleeding during a uterine operation and indicate the location of an intramural pregnancy, helping surgeons to complete the operation successfully.

Outcomes:

The patient recovered quickly and was discharged on the 4th day after surgery, with a significant decrease in human chorionic gonadotrophin (HCG) levels from 14,792.26 mIU/mL before surgery to 1071.40 mIU/mL at discharge. During the follow up, her HCG level dropped to 50.90 mIU/mL on the 14th day after the surgery. She monitored the HCG levels intermittently until they fell within the normal range.

Lessons:

Intramural pregnancy is a rare form of ectopic pregnancy, and it is difficult to diagnose early on. This may result in uterine rupture or even life-threatening hemorrhage. If an intramural pregnancy is suspected in early pregnancy, hysteroscopy combined with laparoscopy is advised, and if necessary, low-dose posterior pituitary hormone can enhance uterine contractions and better reveal the position of the gestational sac within the uterine wall.
Nephron-sparing surgery for primary mucinous adenocarcinoma of renal pelvis in horseshoe kidney: A case report
Authors: Li Dapeng , Zhang Wei , Wang Jun , Wang An , Wu Mingming , Wei Yangguang
Published: March 2023

Rationale:

Mucinous adenocarcinoma of the renal pelvis is extremely rare in malignancy of the renal pelvis, and <100 cases have been reported so far. However, horseshoe kidneys appear to be more prone to this mucinous gland metaplasia. Due to the lack of a specific diagnostic basis, it is difficult to confirm the diagnosis before surgery, which is easy to cause misdiagnosis.

Patient concerns:

We report a 64-year-old male patient who found a cystic mass in the left kidney during physical examination. CT examination showed a horseshoe kidney with a cystic mass 9.5 × 8.0 cm in front of the left kidney, lacking obvious diagnostic features.

Diagnosis:

It was misdiagnosed as cystic teratoma before the operation, and was diagnosed as mucinous adenocarcinoma of the renal pelvis through pathological examination after the operation.

Interventions:

Resection of the tumor by nephron-sparing surgery and postoperative chemotherapy.

Outcomes:

No tumor recurrence was found at 6 years of follow-up. After 7 years, the patient had multiple metastases in the abdominal wall and peritoneum, and no tumor recurrence was found in the urinary system. The patient received chemotherapy again and survived well.

Lessons:

The prognosis of nephron-sparing tumor resection for MRAP is not significantly different from that of radical nephroureterectomy + bladder cuff excision. Because it can reduce the risk that patients can not tolerate follow-up chemotherapy due to abnormal renal function after surgery, which may be more beneficial in patients with kidney abnormalities or chronic disease.
Investigating the potential added value of [18F]FDG-PET/CT in long COVID patients with persistent symptoms: a proof of concept study
Authors: Chen Linda L. , van de Burgt Alina , Smit Frits , Audhoe Rowena S. , de Boer Sandra M. , van Velden Floris H.P. , de Geus-Oei Lioe-Fee
Published: March 2023

Objective

Since the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As more and more patients emerge with long COVID who have symptoms of fatigue, myalgia and joint pain, we must examine potential biomarkers to find quantifiable parameters to define the underlying mechanisms and enable response monitoring. The aim of this study is to investigate the potential added value of [18F]FDG-PET/computed tomography (CT) for this group of long COVID patients.

Methods

For this proof of concept study, we evaluated [18F]FDG-PET/CT scans of long COVID patients and controls. Two analyses were performed: semi-quantitative analysis using target-to-background ratios (TBRs) in 24 targets and total vascular score (TVS) assessed by two independent nuclear medicine physicians. Mann–Whitney U-test was performed to find significant differences between the two groups.

Results

Thirteen patients were included in the long COVID group and 25 patients were included in the control group. No significant differences (P < 0.05) were found between the long COVID group and the control group in the TBR or TVS assessment.

Conclusion

As we found no quantitative difference in the TBR or TVS between long COVID patients and controls, we are unable to prove that [18F]FDG is of added value for long COVID patients with symptoms of myalgia or joint pain. Prospective cohort studies are necessary to understand the underlying mechanisms of long COVID.
Intraoperative Factors Modifying the Risk of Postoperative Pulmonary Complications After Living Donor Liver Transplantation
Authors: Oh Eun Jung , Kim Jeayoun , Kim Bo-Guen , Han Sangbin , Ko Justin S. , Gwak Mi Sook , Kim Gaab Soo , Choi Eun Ah , Kang Jiyeon , Park Hye Yun
Published: March 2023

Background.

The relationship between intraoperative anesthetic management and postoperative pulmonary complications (PPCs) after liver transplantation is not fully understood. We aimed to determine the intraoperative contributors to PPC.

Methods.

The retrospectively collected cohort included 605 patients who underwent living donor liver transplantation. PPCs comprised respiratory failure, respiratory infection, pulmonary edema, atelectasis (at least moderate degree), pneumothorax, and pleural effusion (at least moderate degree). The presence and type of PPC were evaluated by 2 pulmonary physicians. Logistic regression analysis was performed to determine the association between perioperative variables and PPC risk.

Results.

Of the 605 patients, 318 patients (52.6%) developed 486 PPCs. Multivariable analysis demonstrated that PPC risk decreased with low tidal volume ventilation (odds ratio [OR] 0.62 [0.41-0.94], P = 0.023) and increased with greater driving pressure at the end of surgery (OR 1.08 [1.01-1.14], P = 0.018), prolonged hypotension (OR 1.85 [1.27-2.70], P = 0.001), and blood albumin level ≤3.0 g/dL at the end of surgery (OR 2.43 [1.51-3.92], P < 0.001). Survival probability at 3, 6, and 12 mo after transplantation was 91.2%, 89.6%, and 86.5%, respectively, in patients with PPCs and 98.3%, 96.5%, and 93.4%, respectively, in patients without PPCs (hazard ratio 2.2 [1.3-3.6], P = 0.004). Graft survival probability at 3, 6, and 12 mo after transplantation was 89.3%, 87.1%, and 84.3%, respectively, in patients with PPCs and 97.6%, 95.8%, and 92.7%, respectively, in patients without PPCs (hazard ratio 2.3 [1.4-3.7], P = 0.001).

Conclusions.

We found that tidal volume, driving pressure, hypotension, and albumin level during living donor liver transplantation were significantly associated with PPC risk. These data may help determine patients at risk of PPC or develop an intraoperative lung-protective strategy for liver transplant recipients.
Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation
Authors: Subramaniam Kathirvel , Loor Gabriel , Chan Ernest G. , Bottiger Brandi A. , Ius Fabio , Hartwig Matthew G. , Daoud Daoud , Zhang Qianzi , Wei Qi , Villavicencio-Theoduloz Mauricio A. , Osho Asishana A. , Chandrashekaran Satish , Noguchi Machuca Tiago , Van Raemdonck Dirk , Neyrinck Arne , Toyoda Yoshiya , Kashem Mohammed A. , Huddleston Stephen , Ryssel Naomi R. , Sanchez Pablo G.
Published: March 2023

Background.

In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes.

Methods.

The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT.

Results.

We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1–4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly (P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001).

Conclusions.

In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.
Multicenter Validation of a Urine CXCL10 Assay for Noninvasive Monitoring of Renal Transplants
Authors: Ho Julie , Schaub Stefan , Jackson Annette M. , Balshaw Robert , Carroll Robert , Cun Sylvia , De Serres Sacha A. , Fantus Daniel , Handschin Joelle , Hönger Gideon , Jevnikar Anthony M. , Kleiser Marc , Lee Jar-How , Li Yan , Nickerson Peter , Pei Rui , Pochinco Denise , Shih Remi , Trinh Michael , Wang Jason , Nguyen Julie , Knechtle Stuart
Published: March 2023

Background.

Urine CXCL10 (C-X-C motif chemokine ligand 10, interferon gamma-induced protein 10 [IP10]) outperforms standard-of-care monitoring for detecting subclinical and early clinical T-cell–mediated rejection (TCMR) and may advance TCMR therapy development through biomarker-enriched trials. The goal was to perform an international multicenter validation of a CXCL10 bead-based immunoassay (Luminex) for transplant surveillance and compare with an electrochemiluminescence-based (Meso Scale Discovery [MSD]) assay used in transplant trials.

Methods.

Four laboratories participated in the Luminex assay development and evaluation. Urine CXCL10 was measured by Luminex and MSD in 2 independent adult kidney transplant trial cohorts (Basel and TMCT04). In an independent test and validation set, a linear mixed-effects model to predict (log10-transformed) MSD CXCL10 from Luminex CXCL10 was developed to determine the conversion between assays. Net reclassification was determined after mathematical conversion.

Results.

The Luminex assay was precise, with an intra- and interassay coefficient of variation 8.1% and 9.3%; showed modest agreement between 4 laboratories (R 0.96 to 0.99, P < 0.001); and correlated with known CXCL10 in a single- (n = 100 urines, R 0.94 to 0.98, P < 0.001) and multicenter cohort (n = 468 urines, R 0.92, P < 0.001) but the 2 assays were not equivalent by Passing–Bablok regression. Linear mixed-effects modeling demonstrated an intercept of −0.490 and coefficient of 1.028, showing Luminex CXCL10 are slightly higher than MSD CXCL10, but the agreement is close to 1.0. After conversion of the biopsy thresholds, the decision to biopsy would be changed for only 6% (5/85) patients showing acceptable reclassification.

Conclusions.

These data demonstrate this urine CXCL10 Luminex immunoassay is robust, reproducible, and accurate, indicating it can be readily translated into clinical HLA laboratories for serial posttransplant surveillance.
Cardiovascular Outcomes in De Novo Kidney Transplant Recipients Receiving Everolimus and Reduced Calcineurin Inhibitor or Standard Triple Therapy: 24-month Post Hoc Analysis From TRANSFORM Study
Authors: Sommerer Claudia , Legendre Christophe , Citterio Franco , Watarai Yoshihiko , Oberbauer Rainer , Basic-Jukic Nikolina , Han Jackie , Gawai Apurva , Bernhardt Peter , Chadban Steve
Published: March 2023

Background.

The comparative impact of everolimus (EVR)-based regimens versus standard of care (mycophenolic acid+standard calcineurin inhibitor [MPA+sCNI]) on cardiovascular outcomes in de novo kidney transplant recipients (KTRs) is poorly understood. The incidence of major adverse cardiac events (MACEs) in KTRs receiving EVR+reduced CNI (rCNI) or MPA+sCNI from the TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen study was evaluated.

Methods.

The incidence of MACE was determined for all randomized patients receiving at least 1 dose of the study drug. Factors associated with MACEs were determined by logistic regression. Risk of MACE out to 3 y post-study was calculated using the Patient Outcome in Renal Transplantation equation.

Results.

MACE occurred in 81 of 1014 (8.0%; EVR+rCNI) versus 89 of 1012 (8.8%; MPA+sCNI) KTRs (risk ratio, 0.91 [95% confidence interval [CI], 0.68-1.21]). The incidence of circulatory death, myocardial infarction, revascularization, or angina was similar between the arms. Incidence of MACE was similar between EVR+rCNI and MPA+sCNI arms with a higher incidence in prespecified risk groups: older age, pretransplant diabetes (15.1% versus 15.9%), statin use (8.5% versus 10.8%), and low estimated glomerular filtration rate (Month 2 estimated glomerular filtration rate <30 versus >60 mL/min/1.73 m2; odds ratio, 2.23 [95% CI, 1.02-4.86]; P = 0.044), respectively. Predicted risk of MACE within 3 y of follow-up did not differ between the treatment arms.

Conclusions.

Cardiovascular morbidity and mortality were similar between de novo KTRs receiving EVR+rCNI and MPA+sCNI. EVR+rCNI is a viable alternative to the current standard of care in KTRs.
Memory and Consciousness—Usually in Tandem but Sometimes Apart
Authors: Madan Christopher R.
Published: March 2023

Episodic memory, the ability to remember specific events from one’s personal past, has been the subject of research for several decades, with a particular emphasis on its relationship with consciousness. In the December 2022 issue of Cognitive and Behavioral Neurology, Budson, Richman, and Kensinger shed new light on this complex topic with a comprehensive exploration of consciousness. In this commentary, I present three propositions about the relationship between episodic memory and consciousness: (1) Episodic memory is usually associated with conscious retrieval; (2) it is possible to have consciousness without episodic memory; and (3) episodic memory can be accessed without conscious retrieval. Drawing from studies conducted with nonhuman animals, I provide evidence to support each of these propositions and discuss how they relate to the theory presented by Budson et al (2000). Although some of my propositions differ from their views, their work has been valuable in stimulating ongoing discussions to advance our understanding of memory.
A Selective Hand Posture Apraxia in an Individual With Posterior Cortical Atrophy and Probable Corticobasal Syndrome
Authors: Omori Tomohiro , Funayama Michitaka , Anamizu Sachiko , Ishikawa Mei , Niida Richi , Tabuchi Hajime
Published: March 2023

A selective impairment for making hand postures that are required to use specific tools has rarely been reported in individuals with acquired brain injury, and such an impairment has not been documented at all in individuals with degenerative disorders. We describe an individual with posterior cortical atrophy and probable corticobasal syndrome who was unable to use tools because of an inability to make the proper hand posture required for each tool. This individual was, however, able to use the tools properly once her hand postures were corrected, and her ability to manipulate the tools (ie, timing, arm posture, and amplitude) was intact. Also, she had no difficulty with a test of her manipulation knowledge. Areas of hypoperfusion observed by single-photon emission computerized tomography included the anterior intraparietal sulcus in the left parietal lobe, which is an area that has been proposed to control hand postures. This selective impairment might be explained by the reasoning-based hypothesis for apraxia, which attributes hand posture errors in the absence of manipulation errors to dysfunction in one of the three independent pathways that subserve tool use, rather than the manipulation-based hypothesis for apraxia, which attributes hand posture errors to impaired manipulation knowledge. This is the first case with a degenerative disorder that revealed a selective impairment for making hand postures for tool use, which might be explained mainly by apraxia of hand postures along with visuospatial dysfunction (simultanagnosia) and/or sensory disturbance.
Emergence of carbapenem-resistant Pseudomonas alcaligenes and Pseudomonas paralcaligenes clinical isolates with plasmids harbouring bla
IMP-1 in Japan
Authors: Ono Emi , Tohya Mari , Tada Tatsuya , Hishinuma Tomomi , Watanabe Shin , Kuwahara-Arai Kyoko , Kirikae Teruo
Published: March 2023

Introduction. The emergence of carbapenem-resistant

Pseudomonas

species producing metallo-β-lactamase (MBL) has become a serious medical problem worldwide. IMP-type MBL was firstly detected in 1991 in Japan. Since then, it has become one of the most prevalent types of MBLs.

Hypothesis/Gap statement. Avirulent species of

Pseudomonas

, such as

Pseudomonas alcaligenes

, function as reservoirs of drug resistance-associated genes encoding carbapenemases in clinical settings.

Methodology. Active surveillance for carbapenem-resistant Gram-negative pathogens was conducted in 2019 at a hospital in Tokyo, Japan. Of the 543 samples screened for carbapenem-resistant isolates, 2 were species of

Pseudomonas

. One was from a stool sample from a medical staff member, and the other was from a stool sample from a hospitalized patient.

Results. Whole-genome sequencing showed that the former isolate was a strain of

P. alcaligenes

, and the latter was a strain of Pseudomonas paralcaligenes, a species close to

P. alcaligenes

. Both isolates were resistant to all carbapenems and harboured bla
IMP-1 genes encoding IMP-1 MBL, which conferred resistance to carbapenems. The bla
IMP-1 genes of

P. alcaligenes

and P. paralcaligenes were located on the plasmids, pMRCP2, 323125 bp in size, and pMRCP1333, 16592 bp in size, respectively. The sequence of 82 % of pMRCP2 was 92 % similar to the sequence of a plasmid of

P. aeruginosa

PA83, whereas the sequence of 79 % of pMRCP1333 was >95 % similar to the sequence of a plasmid of

Achromobacter xylosoxidans

FDAARGOS 162. The genomic environments surrounding the bla
IMP-1 of pMRCP2 and pMRCP1333 differed completely from each other.

Conclusions. These results indicate that the two isolates acquired bla
IMP-1 from different sources and that

P. alcaligenes

and P. paralcaligenes function as vectors and reservoirs of carbapenem-resistant genes in hospitals.
Analyses of vaccine-specific circulating and bone marrow-resident B cell populations reveal benefit of delayed vaccine booster dosing with blood-stage malaria antigens
Authors: Barrett JR , Silk SE , Mkindi CG , Kwiatkowska KM , Hou MM , Lias AM , Kalinga WF , Mtaka IM , McHugh K , Bardelli M , Davies H , King LDW , Edwards NJ , Chauhan VS , Mukherji P , Rwezaula S , Chitnis CE , Olotu AI , Minassian AM , Draper SJ , Nielsen CM
Published: March 2023

We have previously reported primary endpoints of a clinical trial testing two vaccine platforms for delivery ofPlasmodium vivaxmalaria DBPRII: viral vectors (ChAd63, MVA) and protein/adjuvant (PvDBPII with 50µg Matrix-M™ adjuvant). Delayed boosting was necessitated due to trial halts during the pandemic and provides an opportunity to investigate the impact of dosing regimens. Here, using flow cytometry – including agnostic definition of B cell populations with the clustering tool CITRUS – we report enhanced induction of DBPRII-specific plasma cell and memory B cell responses in protein/adjuvant versus viral vector vaccinees. Within protein/adjuvant groups, delayed boosting further improved B cell immunogenicity as compared to a monthly boosting regimen. Consistent with this, delayed boosting also drove more durable anti-DBPRII serum IgG. In an independent vaccine clinical trial with theP. falciparummalaria RH5.1 protein/adjuvant (50µg Matrix-M™) vaccine candidate, we similarly observed enhanced circulating B cell responses in vaccinees receiving a delayed final booster. Notably, a higher frequency of vaccine-specific (putatively long-lived) plasma cells were detected in the bone marrow of these delayed boosting vaccinees by ELISPOT and correlated strongly with serum IgG.

Finally, following controlled human malaria infection withP. vivaxparasites in the DBPRII trial,in vivogrowth inhibition was observed to correlate with DBPRII-specific B cell and serum IgG responses. In contrast, the CD4+ and CD8+ T cell responses were impacted by vaccine platform but not dosing regimen, and did not correlate within vivogrowth inhibition in a challenge model. Taken together, our DBPRII and RH5 data suggest an opportunity for dosing regimen optimisation in the context of rational vaccine development against pathogens where protection is antibody-mediated.
A Video Segmentation Pipeline for Assessing changes in Pupil Response to Light After Cannabis Consumption
Authors: Steinhart Benjamin , Brooks-Russell Ashley , Kosnett Michael J. , Subramanian Prem S. , Wrobel Julia
Published: March 2023

Due to long-standing federal restrictions on cannabis-related research, the implications of cannabis legalization on traffic and occupational safety are understudied. Accordingly, there is a need for objective and validated measures of acute cannabis impairment that may be applied in public safety and occupational settings. Pupillary response to light may offer an avenue for detection that outperforms typical sobriety tests and THC concentrations. We developed a video processing and analysis pipeline that extracts pupil sizes during a light stimulus test administered with goggles utilizing infrared videography. The analysis compared pupil size trajectories in response to a light for those with occasional, daily, and no cannabis use before and after smoking. Pupils were segmented using a combination of image pre-processing techniques and segmentation algorithms which were validated using manually segmented data and found to achieve 99% precision and 94% F-score. Features extracted from the pupil size trajectories captured pupil constriction and rebound dilation and were analyzed using generalized estimating equations. We find that acute cannabis use results in less pupil constriction and slower pupil rebound dilation in the light stimulus test.
Gata3 is detrimental to regulatory T cell function in autoimmune diabetes
Authors: Kiaf Badr , Bode Kevin , Schuster Cornelia , Kissler Stephan
Published: March 2023

Regulatory T cells (Tregs) protect against autoimmunity. In type 1 diabetes (T1D), Tregs slow the progression of beta cell autoimmunity within pancreatic islets. Increasing the potency or frequency of Tregs can prevent diabetes, as evidenced by studies in the nonobese diabetic (NOD) mouse model for T1D. We report herein that a significant proportion of islets Tregs in NOD mice expressGata3. The expression ofGata3was correlated with the presence of IL-33, a cytokine known to induce and expand Gata3+Tregs. Despite significantly increasing the frequency of Tregs in the pancreas, exogenous IL-33 was not protective. Based on these data, we hypothesized that Gata3 is deleterious to Treg function in autoimmune diabetes. To test this notion, we generated NOD mice with a Treg-specific deletion ofGata3. We found that deletingGata3in Tregs strongly protected against diabetes. Disease protection was associated with a shift of islet Tregs toward a suppressive CXCR3+Foxp3+population. Our results suggest that islet Gata3+Tregs are maladaptive and that this Treg subpopulation compromises the regulation of islet autoimmunity, contributing to diabetes onset.
ChatGPT in glioma patient adjuvant therapy decision making: ready to assume the role of a doctor in the tumour board?
Authors: Haemmerli Julien , Sveikata Lukas , Nouri Aria , May Adrien , Egervari Kristof , Freyschlag Christian , Lobrinus Johannes A. , Migliorini Denis , Momjian Shahan , Sanda Nicolae , Schaller Karl , Tran Sebastien , Yeung Jacky , Bijlenga Philippe
Published: March 2023

Introduction

ChatGPT, a novel AI-based chatbot, sparked a lot of interest in the scientific community. Complex central CNS tumour cases require multidisciplinary expert recommendations that incorporate multimodal disease information. Thus, the potential of ChatGPT to integrate comprehensive treatment information may be of tremendous benefit for CNS tumour decision-making. We evaluated the ChatGPT recommendations for glioma management by a panel of CNS tumour experts.

Methods

We randomly selected 10 patients with primary CNS gliomas discussed at our institution’s Tumour Board. Patients’ clinical status, surgical, imaging, and immuno-pathology-related information was provided to ChatGPT and seven CNS tumour experts. The chatbot was asked to give the most likely diagnosis, the adjuvant treatment choice, and the regimen while considering the patient’s functional status. The experts rated the AI-based recommendations from 0 (complete disagreement) to 10 (complete agreement). An intraclass correlation agreement (ICC) was used to measure the inter-rater agreement.

Results

Eight patients (80%) met the criteria for glioblastoma and two (20%) were low-grade gliomas. The experts rated the quality of ChatGPT recommendations as poor for diagnosis (median 3, IQR 1-7.8, ICC 0.9, 95% CI 0.7-1.0), good for treatment recommendation (7, IQR 6-8, ICC 0.8, 95% CI 0.4-0.9), good for therapy regimen (7, IQR 4-8, ICC 0.8, 95% CI 0.5-0.9), moderate for functional status consideration (6, IQR 1-7, ICC 0.7, 95% CI 0.3-0.9), and moderate for overall agreement with the recommendations (5, IQR 3-7, ICC 0.7, 95% CI 0.3-0.9). No difference were observed between the glioblastomas and low-grade glioma ratings.

Conclusions

ChatGPT performed poorly in classifying glioma types but was good for adjuvant treatment recommendations as evaluated by CNS Tumour Board experts. Even though the ChatGPT lacks the precision to replace expert opinion, it may become a promising tool to supplement experts, especially in low-resource settings.
Turbulence and blood washout in presence of mitral regurgitation: a computational fluid-dynamics study in the complete left heart
Authors: Bennati Lorenzo , Giambruno Vincenzo , Renzi Francesca , Di Nicola Venanzio , Maffeis Caterina , Puppini Giovanni , Luciani Giovanni Battista , Vergara Christian
Published: March 2023

In this work we performed a computational image-based study of blood dynamics in the whole left heart, both in a healthy subject and in a patient with mitral valve regurgitation (MVR). We elaborated dynamic cine-MRI images with the aim of reconstructing the geometry and the corresponding motion of left ventricle, left atrium, mitral and aortic valves, and aortic root of the subjects. This allowed us to prescribe such motion to computational blood dynamics simulations where, for the first time, the whole left heart motion of the subject is considered, allowing us to obtain reliable subject-specific information.

The final aim is to investigate and compare between the subjects the occurrence of turbulence and the risk of hemolysis and of thrombi formation. In particular, we modeled blood with the Navier-Stokes equations in the Arbitrary Lagrangian-Eulerian framework, with a Large Eddy Simulation model to describe the transition to turbulence and a resistive method to manage the valve dynamics, and we used a Finite Elements discretization implemented in an in-house code for the numerical solution.

Our results highlighted that the regurgitant jet in the MVR case gave rise to a large amount of transition to turbulence in the left atrium resulting in a higher risk of formation of hemolysis. Moreover, MVR promoted a more complete washout of stagnant fiows in the left atrium during the systolic phase and in the left ventricle apex during diastole.

NEW & NOTEWORTHY

Reconstruction from cine-MRI images of geometries and motion of the left heart (left atrium and ventricle, aortic root, aortic and mitral valve) of a healthy and mitral regurgitant patient.

Prescription of such motion to a complete subject-specific computational fluid-dynamic simulation of the left heart. Investigation of turbulence in a regurgitant scenario.

Study of the mechanisms of prevention from stagnant flows and hemolysis formation in the atrium.
Comparative transcriptome analysis in contrasting finger millet (Eleusine coracana(L.) Gaertn) genotypes for heat stress
Authors: Goyal Etika , Amit Singh Kumar , Mahajan Mahesh Mohanrao , Kanika Kumar
Published: March 2023

Eleusine coracana(L.) Gaertn is a crucial C4species renowned for its stress robustness and nutritional significance. Because of its adaptability traits, finger millet (ragi) is a storehouse of critical genomic resources for crop improvement. However, more knowledge about this crop’s molecular responses to heat stress must be gained. Hence, in the present study, we generated RNA seq data from the leaf tissue of the finger millet to observe the physiological changes and gene expression study in heat-sensitive (KJNS-46) and heat-tolerant (PES-110) genotypes of Ragi in response to high temperatures. On average, each sample generated about 24 million reads. Nearly 684 transcripts were differentially expressed (DEGs) between the heat-stressed samples of both genotypes. Pathway analysis and functional annotation analysis revealed the activation of various genes involved in response to stress, precisely heat, oxidation-reduction process, water deprivation, heat shock protein and transcription factors, calcium, and kinase signaling. The basal regulatory genes, such as bZIP, were involved in response to heat stress, indicating that heat stress activates genes related to basal regulatory processes or housekeeping. A substantial percentage of the DEGs belonged to proteins of unknown functions (PUFs), i.e., uncharacterized. The expression pattern of a few selected DEGs genes was analyzed in both genotypes by quantitative RT-PCR. The present study found some candidate genes and pathways that may confer tolerance to heat stress in ragi. These results will provide valuable information to improve heat tolerance in heat-susceptible agronomically important varieties of ragi and other crop plants.
Bacterial Peptidoglycan as a Food Digestive Signal in the Nematode that Facilitates Adaptation of Animals in Nature
Authors: Hao Fanrui , Liu Huimin , Qi Bin
Published: March 2023

Food availability and usage is a major adaptive force for the successful survival of animals in nature. However, very little is known about the signal from food to activate the hosts digestive system, which facilitates animals to digest more diverse food in nature. Here, by using a food digestion system inC. elegans, we discover that bacterial peptidoglycan (PGN) is a unique food signal that activates animals to digest inedible food. We find that PGN was sensed by a conserved intestinal glycosylated protein (BCF-1) in nematodes via direct interaction, which promoted food digestion through inhibiting the mitochondrial unfolded protein response (UPRmt). Moreover, constitutive activation of UPRmtis sufficient to inhibit food digestion. Thus, our study reveals how bacterial PGN, as a common digestion cue, activates the food digestive system through interacting with a conserved glycosylated protein, which facilitates adaptation of the host animals by increasing ability to consume a wide range of foods in their natural environment.
On the interaction of replication and transcriptional regulation
Authors: Gemo Pietro , Brilli Matteo
Published: March 2023

DNA replication introduces a gradient of gene copy numbers, and in Bacteria it affects gene expression accordingly. InE. coliand other species, the slope of the gradient averaged over the population can be predicted on the basis of its relationship with growth rate. In this work we integrated this growth- and position-dependent gradient into a classical transcriptional regulation model, to highlight their interaction. The theoretical treatment of our model highlights that the sensitivity to transcription factor-mediated regulations acquires an additional dimension related to the position of a locus on the oriter axis and to division time. This reinforces the idea of replication as an additional layer in gene regulation. We highlight here that replication- and transcription factor-mediated regulations can in theory work in concert or counteract each other, and we discuss why this is important from an evolutionary point of view with respect to both steady state transcript abundance and its variance across conditions. Finally, we note that this treatment may improve the estimation of kinetic parameters for transcription factor activity using RNA-seq data, and the estimation of the dispersion factor in differential gene expression analysis when division time across conditions changes significantly.
Manifold Learning Enables Interpretable Analysis of Raman Spectra from Extracellular Vesicle and Other Mixtures
Authors: Kazemzadeh Mohammadrahim , Martinez-Calderon Miguel , Otupiri Robert , Artuyants Anastasiia , Lowe Moi M. , Ning Xia , Reategui Eduardo , Schultz Zachary D. , Xu Weiliang , Blenkiron Cherie , Chamley Lawrence W. , Broderick Neil G.R. , Hisey Colin L.
Published: March 2023

Extracellular vesicles (EVs) have emerged as promising diagnostic and therapeutic candidates in many biomedical applications. However, EV research continues to rely heavily on in vitro cell cultures for EV production, where the exogenous EVs present in fetal bovine (FBS) or other required serum supplementation can be difficult to remove entirely. Despite this and other potential applications involving EV mixtures, there are currently no rapid, robust, inexpensive, and label-free methods for determining the relative concentrations of different EV subpopulations within a sample. In this study, we demonstrate that surface-enhanced Raman spectroscopy (SERS) can biochemically fingerprint fetal bovine serum-derived and bioreactor-produced EVs, and after applying a novel manifold learning technique to the acquired spectra, enables the quantitative detection of the relative amounts of different EV populations within an unknown sample. We first developed this method using known ratios of Rhodamine B to Rhodamine 6G, then using known ratios of FBS EVs to breast cancer EVs from a bioreactor culture. In addition to quantifying EV mixtures, the proposed deep learning architecture provides some knowledge discovery capabilities which we demonstrate by applying it to dynamic Raman spectra of a chemical milling process. This label-free characterization and analytical approach should translate well to other EV SERS applications, such as monitoring the integrity of semipermeable membranes within EV bioreactors, ensuring the quality or potency of diagnostic or therapeutic EVs, determining relative amounts of EVs produced in complex co-culture systems, as well as many Raman spectroscopy applications.
A bird’s-eye view: Evaluating drone imagery for the detection and monitoring of endangered and invasive day gecko species
Authors: Dubos Nicolas , Porcel Xavier , Roesch Markus A. , Claudin Juan , Pinel Romain , Probst Jean-Michel , Deso Gregory
Published: March 2023

Herpetofauna monitoring can be strongly limited by terrain accessibility, impeding our understanding of species ecology and thus challenging their conservation. This is particularly true for species living in the canopy, on cliffs or in dense vegetation. Remote sensing imagery may fill this gap by offering a cost-effective monitoring approach allowing to improve species detection in inaccessible areas. We investigated the applicability of drone-based monitoring for a Critically Endangered insular gecko (Phelsuma inexpectata) and two invasive alien species representing a risk for the former (P. grandisandP. laticauda). We determined the approach distance before inducing behavioural response caused by the drone’s presence. All three study species showed no reaction to the drone’s presence until very close distances (mean distance forP. inexpectata: 33.8 cm;P. grandis: 21.9 cm;P. laticauda: 26.4 cm). We then performed horizontal and vertical approaches, taking photos every meter starting at 10 m away from the canopy edge to determine an optimal distance for detection while ensuring species-level identification. We examined a total of 328 photos. We found a bimodality in the number of detected geckos, with different individuals recorded between short and intermediate distances. Therefore, we recommend taking photos at two distances of 2–2.5 m and 5 m away from the canopy, ideally facing away from the sun and in low wind conditions. We encourage the application of our methodology forPhelsumaspp., but also for other species of similar size and ecology to improve detection in inaccessible areas.