bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin K – sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity
Authors: Mladěnka Přemysl , Macáková Kateřina , Kujovská Krčmová Lenka , Javorská Lenka , Mrštná Kristýna , Carazo Alejandro , Protti Michele , Remião Fernando , Nováková Lucie ,   the OEMONOM researchers and collaborators
Published: July 2021

Vitamin K is traditionally connected with blood coagulation, since it is needed for the posttranslational modification of 7 proteins involved in this cascade. However, it is also involved in the maturation of another 11 or 12 proteins that play different roles, encompassing in particular the modulation of the calcification of connective tissues. Since this process is physiologically needed in bones, but is pathological in arteries, a great deal of research has been devoted to finding a possible link between vitamin K and the prevention of osteoporosis and cardiovascular diseases. Unfortunately, the current knowledge does not allow us to make a decisive conclusion about such a link. One possible explanation for this is the diversity of the biological activity of vitamin K, which is not a single compound but a general term covering natural plant and animal forms of vitamin K (K1 and K2) as well as their synthetic congeners (K3 and K4). Vitamin K1 (phylloquinone) is found in several vegetables. Menaquinones (MK4–MK13, a series of compounds known as vitamin K2) are mostly of a bacterial origin and are introduced into the human diet mainly through fermented cheeses. Current knowledge about the kinetics of different forms of vitamin K, their detection, and their toxicity are discussed in this review.
Genetic epidemiological analysis of hypouricaemia from 4993 Japanese on non-functional variants of URAT1/SLC22A12 gene
Authors: Nakayama Akiyoshi , Kawamura Yusuke , Toyoda Yu , Shimizu Seiko , Kawaguchi Makoto , Aoki Yuka , Takeuchi Kenji , Okada Rieko , Kubo Yoko , Imakiire Toshihiko , Iwasawa Satoko , Nakashima Hiroshi , Tsunoda Masashi , Ito Keiichi , Kumagai Hiroo , Takada Tappei , Ichida Kimiyoshi , Shinomiya Nariyoshi , Matsuo Hirotaka
Published: July 2021

Objectives

Up to 0.3% of Japanese have hypouricaemia. Most cases appear to result from a hereditary disease, renal hypouricaemia (RHUC), which causes exercise-induced acute kidney injury and urolithiasis. However, to what extent RHUC accounts for hypouricaemia is not known. We therefore investigated its frequency and evaluated its risks by genotyping a general Japanese population.

Methods

A cohort of 4993 Japanese was examined by genotyping the non-functional variants R90H (rs121907896) and W258X (rs121907892) of URAT1/SLC22A12, the two most common causative variants of RHUC in Japanese.

Results

Participants’ fractional excretion of uric acid and risk allele frequencies markedly increased at lower serum uric acid (SUA) levels. Ten participants (0.200%) had an SUA level ≤2.0 mg/dl and nine had R90H or W258X and were likely to have RHUC. Logistic regression analysis revealed these URAT1 variants to be significantly and independently associated with the risk of hypouricaemia and mild hypouricaemia (SUA ≤3.0 mg/dl) as well as sex, age and BMI, but these URAT1 variants were the only risks in the hypouricaemia population (SUA ≤2.0 mg/dl). W258X was only a risk in males with SUA ≤3.0 mg/dl.

Conclusion

Our study accurately reveals the prevalence of RHUC and provides genetic evidence for its definition (SUA ≤2.0 mg/dl). We also show that individuals with SUA ≤3.0 mg/dl, especially males, are prone to RHUC. Our findings will help to promote a better epidemiological understanding of RHUC as well as more accurate diagnosis, especially in males with mild hypouricaemia.
Compressing audio signals with interactive and cloud-based learning material—a workshop for high-school students
Authors: Wohak Kirsten , Frank Martin
Published: July 2021

Undeniably omnipresent in our everyday lives, electronic signal compression is a classical example that illustrates the ubiquity of mathematics in high-end technology and sciences. When dealing with piles of files, it is essential that each file takes up as little storage space as possible while maintaining quality. The cloud-based—available under a Creative Commons licence—workshop that is described in the following paper addresses this trade-off between quality and compression rate based on the example of audio signals. Here, students use tools from linear algebra to compress music according to their own hearing model which they developed previously. More specifically, they use the basis change (i.e. the Fourier transform) between the time-dependent and frequency-dependent representations of sounds to remove those frequencies from an instrumental piece that are outside of their hearing model. Such mathematical tools may seem out of reach for high-school students, but we demonstrate that they are indeed suited for developing solutions with minimal help.
Characteristics of Gut Microbiome After Traumatic Brain Injury
Authors: Mahajan Charu , Khurana Surbhi , Kapoor Indu , Sokhal Suman , Kumar Subodh , Prabhakar Hemanshu , Mathur Purva , Mani Kalaivani
Published: July 2021

Background:

Preclinical studies have reported significant changes in the gut microbiome after traumatic brain injury (TBI). We hypothesized that TBI induces the growth of Proteobacteria in the human gut. Our primary outcome was to study the profile of the human fecal microbiome after TBI and the secondary outcome was to identify colonization with colistin-resistant and multidrug-resistant pathogens.

Methods:

Consecutive patients with moderate-severe TBI admitted to the neurotrauma-intensive care unit within 48 hours of injury were enrolled into this observational study. Samples from rectal swabs obtained on days 0, 3, and 7 after admission were assessed for microbial growth and antibiotic resistance. Demographic data and variables such as hypotension, blood transfusion, surgery, start of nasogastric feeding, use of antibiotics, length of hospital stay and mortality were noted.

Results:

One hundred one patients were enrolled into this study; 57 (56.4%) underwent surgery, 80 (79.2%) required blood transfusion, 15 (14.9%) had an episode of hypotension, 37 (36.6%) received enteral feed within the first 3 days, and 79 (78.2%) received antibiotics. Rectal microbiological samples were collected from 101, 95, and 85 patients on days 0, 3, and 7, respectively. All organisms isolated at the 3 time-points belonged to the Proteobacteria phylum, with Enterobacteriaceae forming the largest group. Colistin-resistant organisms were found in 17 (16.8%) of 101 patients and multidrug-resistant organisms in 25 (64.1%) of the 39 patients in whom isolates were tested against the entire panel of antimicrobials.

Conclusion:

TBI is associated with widespread colonization with Proteobacteria as early as 48 hours after injury. Colonization with colistin and multidrug-resistant organisms highlights the importance of the judicious use of antibiotics.
The use of modular total knee prostheses in femoral defects in traumatic and revision patients: a prospective case series
Authors: Rady Ahmed Emad , Abdelazim Haytham , Hashem Mohammed H. , El Ghazawy Ahmed K.
Published: July 2021

Background:

Management of distal femoral bone defects represents a great challenge, whether these defects are caused by failed total knee arthroplasties or trauma. One method of management is the use of modular hinged total knee implants with distal femoral replacement, depending on the present defects. Such prostheses can be used in revision surgery, acute comminuted distal femoral fracture, or distal femoral fracture with nonunion. This study aimed to analyze the functional outcome and possible complications of the use of modular total knee prostheses in revision surgery or traumatic injuries in patients with femoral defects.

Methods:

This study was a prospective case series of nononcologic femoral endoprosthetic reconstructions for either revision total knee arthroplasty (TKA) or traumatic femoral defects in eight patients (n=8) from 2015 to 2020. Patient cases were categorized as failed TKA (n=4) or traumatic (n=4). Traumatic patient cases were either distal femoral fractures with nonunion (n=2) or periprosthetic fractures (n=2). Mean follow-up was 2.75 yr (range from 6 mo to 4 yr). Clinical outcomes and ambulatory status (able to walk or not) were assessed. Knee Society Scores (KSS) were calculated, and the range of motion (ROM) was assessed.

Results:

In this group of patients, modular endoprosthetic replacement provided immediate pain relief, early mobilization, and weightbearing. KSS was improved in all patients. ROM was 70 to 90 degrees in four patients, and 90 to 110 degrees in four patients. None of the patients developed soft-tissue infection or implant loosening during the follow-up period.

Conclusions:

Short-term clinical outcomes for the use of modular endoprosthetic total knee implants in the management of distal femoral defects in either traumatic injury or revision surgery result in good functional outcome and patient satisfaction.

Level of Evidence:

Level III.
Adult reconstruction call and prosthetic joint infection (PJI) management patterns across the United States: a cross-sectional study
Authors: Vajapey Sravya P. , Li Mengnai , Glassman Andrew H.
Published: July 2021

Background:

Patients with prosthetic joint infection (PJI) impose a significant burden in total costs, resources consumed, complication rates, and readmission risk. We sought to determine how patients with PJI who were transferred from other hospitals were initially triaged and managed by medical centers across the country.

Methods:

An online survey was sent to fellowship program directors or chiefs of adult reconstruction (AR) divisions at academic medical centers. The survey consisted of 11 multiple-choice questions regarding initial management and disposition of patients with PJI who were transferred from other hospitals. Statistical analysis was performed.

Results:

Of 96 programs queried, 34 institutions responded. All participating programs performed revision arthroplasties. Thirty-three (97.5%) of the 34 programs accepted transfer of patients with PJI, even if the index arthroplasty procedure was done elsewhere. Twenty-eight (82.4%) responded that a fellowship-trained AR surgeon provides initial treatment to transferred patients with PJI, provided patients are not septic or critically ill. If a patient was septic or critically ill, 12 (35.3%) programs responded that the surgeon on call for general orthopaedics would provide the initial treatment for PJI, usually with irrigation and debridement with retention of components and that, once the patient is medically stabilized, a fellowship-trained AR surgeon would assume care. Roughly 44% of the programs that participated in the survey had a dedicated AR call pool.

Conclusions:

There were a variety of models used by academic medical centers for triaging and management of PJI transfer patients. There does not seem to be one single algorithm universally accepted as optimum for initial management of patients.

Level of Evidence:

Level III.
Future of women orthopaedists: signs of optimism in a 3-year follow-up survey
Authors: Fuchs Lee , Oron Amir
Published: July 2021

Background:

Gender diversity in medicine can improve physician-patient interactions. Although the number of female medical students has risen to almost 50%, the relative number of female orthopaedic residents remains low. The reason for so few female applicants to orthopaedic programs remains in question.

Methods:

A web survey was distributed to medical students and interns in Israel in 2015 and again in 2018. The survey included demographic data and a questionnaire. The questionnaire explored reasons for not choosing orthopaedics as a specialty and exposure to musculoskeletal medicine in medical school.

Results:

A total of 371 responses were received, 143 in 2015 and 228 in 2018. The distribution of gender, marital status, student status, and medical schools were similar. Men were more inclined to choose orthopaedics in both years (P=0.004, P=0.044). The major reason for not choosing orthopaedics was “it’s just not interesting.” However, in 2018, there were a significant number of male responders who wanted a more balanced work-life profession (P=0.047).

Conclusions:

Women have given many possible reasons for not choosing orthopaedic surgery, such as wanting a better work-life balance, perceptions of physical strength needed, a closed “boy’s club,” not enough exposure, and lack of female role models, yet most of them replied the field is “just not interesting.” The authors suggest in concordance to the literature that having more opportunity for exposure and more female role models would increase gender diversity in orthopaedics.

Level of Evidence:

Level IV.
Effect of Joint Exposure to Psychosocial and Physical Work Factors on the Incidence of Workplace Injuries
Authors: Colin Régis , Wild Pascal , Paris Christophe , Boini Stéphanie
Published: July 2021

Objective:

To analyze the interaction between physical and psychosocial work factors regarding the workplace injuries incidence among 6900 workers out of a longitudinal survey.

Methods:

Based on responses to questionnaires, we obtained exposure groups respectively for physical factors and for psychosocial factors using hierarchical clustering. We performed multiple Poisson regression model with the workplace injuries incidence during 4 years of follow-up as the outcome and the clusters as the independent variables of interest.

Results:

High psychosocial exposure had a deleterious effect on workplace injuries incidence, which was no longer significant when adjusting for physical factors. The difference in model-based workplace injuries rates between high and low psychosocial exposures seemed to increase (non-significantly) with increasing physical exposure.

Conclusions:

The risk of workplace injuries was highest among workers with high physical exposures regardless of the psychosocial exposures.
Comparison Between Transimpedance Matrix (TIM) Measurement and X-ray Fluoroscopy for Intraoperative Electrode Array Tip Fold-Over Detection
Authors: Klabbers Tim M. , Huinck Wendy J. , Mylanus Emmanuel A. M.
Published: July 2021

Objective:

The aim of this study was to compare Transimpedance Matrix (TIM-) measurement and X-ray fluoroscopy for the intraoperative detection of electrode array tip fold-over in cochlear implant recipients.

Study design:

Retrospective agreement study.

Setting:

Tertiary referral hospital.

Patients:

Forty-two patients (47 ears) consecutively implanted with the Slim Modiolar Electrode.

Interventions:

Five raters, with different levels of clinical experience, individually retrospectively evaluated the TIM-heatmaps and X-ray fluoroscopy images of all patients included in this study for electrode array tip fold-over.

Main Outcome Measures:

Agreement between raters’ individual evaluation and the diagnosis given during clinical intraoperative evaluation for both modalities, as well as the inter-method agreement between TIM-measurement and fluoroscopy, and the inter-rater agreement for both modalities.

Results:

A tip fold-over was found in three of the forty-seven implantations (6.4%) included in this study. The average agreement between raters’ evaluation and the intraoperative evaluation was 88% (Cohens κ = 0.378) for fluoroscopy and 99% (Cohens κ = 0.915) for TIM-measurement. Two raters misdiagnosed at least one tip fold-over as being correctly positioned when evaluating the fluoroscopy images (1/3 and 3/3, respectively). Each of the raters correctly detected all three tip fold-overs using the TIM-heatmaps. The inter-rater agreement for fluoroscopy was classified as “fair” (Fleiss’ κ = 0.286), while the inter-rater agreement for TIM-measurement was classified as “near-perfect” (Fleiss’ κ = 0.850).

Conclusions:

TIM-measurement has a high potential to replace X-ray fluoroscopy for intraoperatively detecting electrode array tip fold-over in cochlear implantation, especially in patients implanted with flexible, precurved arrays.
Polyethylene Glycol 3350 Changes Stool Consistency and the Microbiome but not Behavior of CD1 Mice
Authors: Salman Salman S. , Williams Kent C. , Marte-Ortiz Pedro , Rumpf Wolfgang , Mashburn-Warren Lauren , Lauber Christian L. , Bailey Michael T. , Maltz Ross M.
Published: July 2021

Objectives:

Polyethylene Glycol 3350 (PEG3350) is a laxative commonly used to treat constipation in children. The Food and Drug Administration has received reports of increased anxiety, aggression, and obsessive--compulsive behaviors in children administered PEG3350. Thus, we assessed whether daily administration of PEG3350 leads to anxiety-like behavior in mice.

Methods:

Outbred CD-1 IGS mice were administered either a high or a low dose of PEG3350 via daily oral gavage for 2 weeks. As a laxative comparison and control, additional mice were given a high or low dose of magnesium citrate or vehicle (water). Weight and stool consistency were assessed after each gavage to determine laxative effectiveness. Anxiety-like behaviors were assessed using light/dark, open field, and elevated plus maze (EPM) tests at baseline, after 2 weeks of daily gavage, and after a 2 week washout in experiment 1, and after 2 weeks of daily gavage in experiment 2. Stool samples were collected for microbiome analysis in experiment 2 at baseline, after 2 weeks of daily gavage, and after 2 weeks washout.

Results:

PEG3350 and magnesium citrate significantly changed stool consistency, as well as microbiome alpha and beta diversity. Anxiety-like behaviors were not, however, different in mice administered low or high doses of PEG3350 or magnesium citrate.

Conclusions:

Although changes in stool consistency and the gut microbiome occurred, administration of PEG3350 did not alter anxiety-like behaviors.
2020: Association for Nursing Professional Development’s Year of Resources and Resilience
Authors: Russell Jillian A. , Bodine Jenn
Published: July 2021

The coronavirus pandemic has undoubtedly challenged the nursing professional development community to adeptly navigate unchartered territory to meet the needs of frontline staff. To ease the struggles of its membership, the Association for Nursing Professional Development conducted, summarized, and provided meaningful environmental scanning and just-in-time resources. Numerous resources were created to ensure nursing professional development practitioners were equipped to navigate the challenges presented throughout 2020.
Brief Report: Frailty in Aging People Living With HIV: A Matched Controlled Study
Authors: Lellouche Lionel , Gutierrez Laure-Anne , Leclercq Pascale , Zaegel-Faucher Olivia , Bernard Louis , Vassallo Matteo , Barbuat Claudine , Ozguler Anna , Zins Marie , Nailler Laura , Reynes Jacques , Berr Claudine , Makinson Alain
Published: July 2021

Background:

We compared the prevalence of frailty among aging people living with HIV (PLHIV) with people without HIV from the ANS EP58 HAND 55–70 Study.

Methods:

Cross-sectional multicentric study which consecutively included 200 PLHIV and 1000 people without HIV from the French national CONSTANCES cohort, matched on age, sex, and education level. PLHIV were aged 55–70 years, with a HIV viral load < 50 copies/mL and a lymphocyte T-CD4 level > 200 cells/µL for the last 24 and 12 months, respectively. We measured frailty (>2 items) and prefrailty (one or 2 items) using a proxy of the 5-item Fried score. Multivariate logistic regression was performed to assess the association between HIV and frailty/prefrailty, adjusting for demographic, social, behavioral, and comorbidity confounders.

Results:

Outcome measures were available for 192 PLHIV and 822 people without HIV. The median age was 62 years, and 84.9% were men. Among PLHIV, the median CD4 cell count was 645.5 cells/µL. Prevalence of frailty/prefrailty was 5.73%/57.3% in PLHIV vs. 1.73%/52.2% in people without HIV, respectively. HIV was associated with prefrailty/frailty [odds ratio = 1.89; 95% confidence interval = 1.37 to 2.61), but after adjusting for social and behavioral factors and comorbidities, HIV was not significantly associated with prefrailty/frailty (odds ratio = 1.24; 95% confidence interval: = 0.84 to 1.81). In PLHIV only, frailty/prefrailty was associated with depressive symptomatology, kidney disease, and time since HIV infection.

Conclusions:

Prevalence of frailty is increased in aging PLHIV with well-controlled HIV disease, but other factors than HIV are predominant, particularly depression and comorbidities.
Detection of Diffuse Peritoneal and Omental Metastases From Prostate Cancer With 18F-PSMA-1007 PET/CT
Authors: Ji Xiaowei , Wang Ling , Lin Jie , Tang Kun
Published: July 2021

Diffuse peritoneal and omental infiltration of prostate cancer detected by 18F-PSMA-1007 PET/CT was rarely reported. We report a case of an 80-year-old man who was suspected of prostate carcinoma metastasis and underwent 18F-PSMA-1007 PET/CT for restaging the disease. PET/CT imaging presented intense tracer uptake in the prostate gland, multiple lymph nodes, and bones. Interestingly, we found extremely increased radioactive uptake of diffuse peritoneum and omentum on 18F-PSMA-1007 PET/CT images, which are very rare metastatic sites for prostate cancer.
Secondary Raised Intracranial Pressure After Cranial Vault Remodeling for Isolated Sagittal Craniosynostosis
Authors: Moore Mark H. , Chaisrisawadisuk Sarut , Prasad Vani , Santoreneos Stephen , Molloy Cindy J.
Published: July 2021

The management of sagittal craniosynostosis has evolved over the decades as teams seek to refine their surgical approaches to idealize head shape with the least possible morbidity. Here, the authors identify the incidence of raised intracranial pressure (ICP) and its risk factors, requiring secondary surgical intervention after cranial vault remodeling (CVR) procedure at a single tertiary referral craniofacial unit. A retrospective case-control study was performed on the patients with isolated non-syndromic sagittal craniosynostosis. All patients who underwent CVR in our unit and had a minimum of 1.5 years follow-up were included. One hundred and eighty-four patients (134 male and 50 female) who underwent primary CVR surgery for isolated sagittal craniosynostosis were included. Thirteen patients (7.07%) had clinical evidence of late raised ICP resulting in repeat CVR procedures. Higher incidence of raised ICP in patients who had primary surgery before 6 months than after or at 6 months of age (P = 0.001). There were 23.5%, 5.6%, 3.2%, and 1.9% of secondary raised ICP patients who underwent the primary surgery between 1999–2004, 2005–2010, 2011–2015 and 2016–2018, respectively (P = 0.024). The risk of secondary raised ICP was higher in patients with isolated sagittal craniosynostosis whose primary surgery occurred before the age of 6 months (two times more likely). More extensive CVR can be performed safely in sagittal synostosis with promising outcomes. The late presentation with raised ICP reinforces the importance of long-term multidisciplinary protocol-based follow-up.
The Impact of Transition Readiness and Stress on Patient-Centered Outcomes in Young Adults With Inflammatory Bowel Disease
Authors: Rhodes Kathleen A. , Walker Jean T. , Zhang Lei , Carr Kayla L. , Winters Karen P. , Glover Sarah C.
Published: July 2021

Young adults, 18–35 years of age, account for nearly half of all inflammatory bowel disease emergency department visits annually, costing millions of healthcare dollars and signifying undue pain and suffering. To mitigate this sequela, the study aimed to characterize the relationships between transition readiness (self-management ability), stress, and patient-centered outcomes. Outcomes were defined as disease activity and inflammatory bowel disease-related healthcare utilization (emergency department visits and inpatient hospitalization). This was a descriptive, correlational design via online survey of young adults with inflammatory bowel disease. Participants (n = 284) utilized an estimated 2.77 million healthcare dollars in 12 months. Transition readiness decreased the odds of having consistently active disease and healthcare utilization, with adjusted odds ratio ranging from 6.4 to 10.9 (p < .05). Higher stress levels increased the odds of having consistently active disease and healthcare utilization, with adjusted odds ratio ranging from 9.5 to 10.5 (p < .0001). Twenty-five percent (24.7%) of the variation in transition readiness was explained by changes in stress (p < .0001). Transition readiness and stress impacted all patient-centered outcomes. Stress negatively impacted transition readiness. These results are powerful reminders for healthcare providers to assess and treat stress and support transition readiness in young adults with inflammatory bowel disease. The potential to decrease pain, suffering, and healthcare cost is enormous.
Incidence, Clinical Characteristics and Outcomes of Early Hyperbilirubinemia in Critically Ill Patients: Insights From the MARS Study
Authors: Juschten Jenny , Bos Lieuwe D. J. , de Grooth Harm-Jan , Beuers Ulrich , Girbes Armand R. J. , Juffermans Nicole P. , Loer Stephan A. , van der Poll Tom , Cremer Olaf L. , Bonten Marc J. M. , Schultz Marcus J. , Tuinman Pieter Roel ,   for the MARS∗ consortium
Published: July 2021

Objective:

To investigate the incidence, clinical characteristics and outcomes of early hyperbilirubinemia in critically ill patients.

Design and Setting:

This is a post hoc analysis of a prospective multicenter cohort study.

Patients:

Patients with measured bilirubin levels within the first 2 days after ICU admission were eligible. Patients with liver cirrhosis were excluded.

Endpoints:

The primary endpoint was the incidence of early hyperbilirubinemia, defined as bilirubin ≥33 μmol/L within 2 days after ICU admission. Secondary endpoints included clinical characteristics of patients with versus patients without early hyperbilirubinemia, and outcomes up to day 30.

Results:

Of 4,836 patients, 559 (11.6%) patients had early hyperbilirubinemia. Compared to patients without early hyperbilirubinemia, patients with early hyperbilirubinemia presented with higher severity of illness scores, and higher incidences of sepsis and organ failure. After adjustment for confounding variables, early hyperbilirubinemia remained associated with mortality at day 30 (odds ratio, 1.31 [95%–confidence interval 1.06–1.60]; P = 0.018). Patients with early hyperbilirubinemia and thrombocytopenia (interaction P-value = 0.005) had a higher likelihood of death within 30 days (odds ratio, 2.61 [95%–confidence interval 2.08–3.27]; P < 0.001) than patients with early hyperbilirubinemia and a normal platelet count (odds ratio, 1.09 [95%–confidence interval 0.75–1.55]; P = 0.655).

Conclusions:

Early hyperbilirubinemia occurs frequently in the critically ill, and these patients present with higher disease severity and more often with sepsis and organ failures. Early hyperbilirubinemia has an association with mortality, albeit this association was only found in patients with concomitant thrombocytopenia.
Chitinophaga silvatica sp. nov., isolated from forest soil, and reclassification of Chitinophaga extrema as a later heterotypic synonym of Chitinophaga solisilvae
Authors: Yao Yuxin , Zhong Xinhua , Li Huixian , Fan Weilin , Xiang Qi , Huang Yadong
Published: July 2021

A novel bacterial strain, designated K2CV101002-2T, was isolated from forest soil collected at Dinghushan Biosphere Reserve, Guangdong Province, PR China. Phylogenetic analyses based on 16S rRNA gene sequences showed that it belonged to the genus

Chitinophaga

and was most closely related to

Chitinophaga terrae

KP01T (99.0 %), followed by

Chitinophaga extrema

Mgbs1T (98.3 %) and

Chitinophaga solisilvae

O9T (98.1 %). The draft genome sequence was 6.8 Mb long with a relative low G+C content of 39.8 mol%. The average nucleotide identity and digital DNA–DNA hybridization values between the novel strain and closely related type strains were 71.4‒76.2 % and 18.4‒19.6 %, respectively. Meanwhile the corresponding values between

C. extrema

Mgbs1T and

C. solisilvae

O9T were 98.6 and 88.1 %, respectively. The novel strain contained iso-C15:0, C16:1
ω5c and iso-C17:0 3-OH as the major fatty acids and MK-7 as the predominant respiratory quinone. The polyphasic study clearly supported that strain K2CV101002-2T represents a new species of the genus

Chitinophaga

, for which the name Chtinophaga silvatica sp. nov. (type strain K2CV101002-2T=GDMCC 1.1288T=JCM 32696T) is proposed. In addition,

Chitinophaga extrema

Goh et al. 2020 should be taken as a later heterotypic synonym of

Chitinophaga solisilvae

Ping et al. 2020.
Cross-sectional cycle threshold values reflect epidemic dynamics of COVID-19 in Madagascar
Authors: Andriamandimby Soa Fy , Brook Cara E. , Razanazatovo Norosoa , Rakotondramanga Jean-Marius , Rasambainarivo Fidisoa , Raharimanga Vaomalala , Razanajatovo Iony Manitra , Mangahasimbola Reziky , Razafindratsimandresy Richter , Randrianarisoa Santatra , Bernardson Barivola , Rabarison Joelinotahiana Hasina , Randrianarisoa Mirella , Nasolo Frédérick Stanley , Rabetombosoa Roger Mario , Randremanana Rindra , Héraud Jean-Michel , Dussart Philippe
Published: July 2021

As the national reference laboratory for febrile illness in Madagascar, we processed samples from the first epidemic wave of COVID-19, between March and September 2020. We fit generalized additive models to cycle threshold (Ct) value data from our RT-qPCR platform, demonstrating a peak in high viral load, low-Ctvalue infections temporally coincident with peak epidemic growth rates estimated in real time from publicly-reported incidence data and retrospectively from our own laboratory testing data across three administrative regions. We additionally demonstrate a statistically significant effect of duration of time since infection onset on Ctvalue, suggesting that Ctvalue can be used as a biomarker of the stage at which an individual is sampled in the course of an infection trajectory. As an extension, the population-level Ctdistribution at a given timepoint can be used to estimate population-level epidemiological dynamics. We illustrate this concept by adopting a recently-developed, nested modeling approach, embedding a within-host viral kinetics model within a population-level Susceptible-Exposed-Infectious-Recovered (SEIR) framework, to mechanistically estimate epidemic growth rates from cross-sectional Ctdistributions across three regions in Madagascar. We find that Ct-derived epidemic growth estimates slightly precede those derived from incidence data across the first epidemic wave, suggesting delays in surveillance and case reporting. Our findings indicate that public reporting of Ctvalues could offer an important resource for epidemiological inference in low surveillance settings, enabling forecasts of impending incidence peaks in regions with limited case reporting.
Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii strains in Belgian acute-care hospitals
Authors: Valcek Adam , Bogaerts Pierre , Denis Olivier , Huang Te-Din , Van der Henst Charles
Published: July 2021

Synopsis

Objectives

To describe the genotypic epidemiological distribution and the antibiotic resistance mechanisms of recent carbapenem-resistant Acinetobacter baumannii (CRAb) strains recovered from clinical samples in Belgium.

Methods

A total of 40 clinical isolates of CRAb collected by the national reference center from 19 acute-care hospitals through national microbiological surveillance in 2014 and 2017 were analysed in this study. The isolates were tested for antimicrobial susceptibility by broth microdilution and determined for carbapenemase-encoding genes by multiplex PCR targeting major carbapenemases families. Isolates were subjected to whole-genome sequencing (WGS) with Illumina technology and the complete chromosomal sequences were de novo assembled. Genome analysis was performed to identify intrinsic and acquired resistance determinants and to characterize clonal lineage according to the sequence type (ST).

Results

All 40 isolates were resistant to carbapenems and exhibited extensively drug-resistant phenotype with blaOXA-23 (n=29) being the most abundant detected acquired AMR gene with 38 isolates encoding at least two different types of OXA enzymes. The majority of the isolates were globally disseminated clones of ST2 (n=25) while less frequent sequence types such as ST636 (n=6), ST1 (n=3), ST85 (n=2) and per one isolate from ST604, ST215, ST158 and ST78 were also detected.

Conclusions

We have detected extensively drug-resistant globally occurring clones of A. baumannii ST1 and ST2 throughout Belgium as well as other sporadic ST including ST636 causing local outbreaks. Our results show the presence of high-risk clones of A. baumannii with common travel importation and the crucial need of constant surveillance.
Excess mortality analysis for Germany for all three COVID-19 waves in 2020 - 2021
Authors: Weber Alexej
Published: July 2021

Background and Aims

The excess mortality has been used as a metric to estimate the impact of COVID-19 across countries. For Germany, we observe that during the second half of the first and second COVID-19 waves, the COVID-19 deaths are significantly higher than the excess mortality. We attribute the difference to the pre-dying effect. We then compare the excess mortality to the official COVID-19 death numbers and calculate the infection fatality rates (IFRs) and the percentage of infected individuals from excess mortality for different age bands. We also compare the impact of COVID-19 to past influenza waves and analyze the vaccination effect on excess mortality.

Methods

We forecast the baseline mortality from official data on deaths in Germany. Distributing a part of excess mortality into the near future, we lower the baseline simulating the pre-dying effect. From the observed mortality deficit, we estimate the percentage of infected individuals and then estimate the age-dependent IFRs.

Results

In the first wave, we find an overall excess mortality of ca. 8 000. For the second wave, the overall excess mortality adds up to ca. 56 000. We find, that the pre-dying effect explains the difference between the official COVID-19 deaths and excess mortality in the second half of the waves to a high degree. Attributing the whole excess mortality to COVID-19, we find that the IFRs are significantly higher in the second wave. In the third wave, the overall excess mortality is ca. 5 000. We find an excess mortality in mid-age bands which cannot be explained by the official COVID-19 deaths. For the senior band 80+, we find results in favor of a strong and positive vaccination effect for the third COVID-19 wave.

Conclusions

We conclude that in the first and second COVID-19 waves, the COVID-19 deaths explain almost all excess mortality when the pre-dying effect is taken into account. In the third wave in 2021, the excess mortality is not very pronounced for the 80+ age band, probably due to vaccination. The partially unvaccinated 40-80 age group experiences a pronounced excess mortality in the third wave while there are too few official COVID-19 deaths to explain the excess. The no-vaccination scenario for the 80+ age band results in a similarly high excess mortality as for the more younger age bands, suggesting a very positive vaccination effect on reduction of COVID-19 deaths.
COVID-19 deaths and hospitalizations averted by rapid vaccination rollout in the United States
Authors: Moghadas Seyed M. , Sah Pratha , Fitzpatrick Meagan C. , Shoukat Affan , Pandey Abhishek , Vilches Thomas N. , Singer Burton H. , Schneider Eric C. , Galvani Alison P.
Published: July 2021

Importance

Randomized clinical trials have shown that the COVID-19 vaccines currently approved in the US are highly efficacious. However, more evidence is needed to understand the population-level impact of the US vaccination rollout in the face of the changing landscape of COVID-19 pandemic in the US, including variants with higher transmissibility and immune escape.

Objective

To quantify the population-level impact of the US vaccination campaign in averting cases, hospitalizations and deaths from December 12, 2020 to June 28, 2021.

Design

Age-stratified agent-based model which included transmission dynamics of the Alpha, Gamma and Delta variants in addition to the original Wuhan-1 variant.

Setting

Our model was calibrated to COVID-19 outbreak and vaccine rollout in the US. Model predictions were made at the country level.

Participants

Simulated age-stratified population representing US demographics.

Main Outcomes and Measures

Cases, hospitalizations and deaths averted by vaccination against COVID-19 in the US, compared to the counterfactuals of no vaccination and vaccination administered at half the actual pace.

Results

The swift vaccine rollout in the US curbed a potential resurgence of cases in April 2021, which would have been otherwise fuelled by the Alpha variant. Compared to the scenario without vaccines, we estimated that the actual vaccination program averted more than 26 million cases, 1.2 million hospitalizations and saved 279,000 lives. A vaccination campaign with half the actual rollout rate would have led to an additional 460,000 hospitalizations and 121,000 deaths.

Conclusions and Relevance

The COVID-19 vaccination campaign in the US has had an extraordinary impact on reducing disease burden despite the emergence of highly transmissible variants. These findings highlight that the pace of vaccination was essential for mitigating COVID-19 in the US, and underscore the urgent need to close the vaccine coverage gaps in communities across the country.

Key Points

Question

How effective was the United States (US) vaccination campaign in suppressing COVID-19 burden?

Findings

The vaccination campaign was highly effective in curbing the COVID-19 outbreak in the US. We estimated that the vaccine rollout saved over 275,000 lives and averted 1.2 million hospitalizations.

Meaning

The swift vaccine rollout in the US averted a remarkable number of cases, hospitalizations and deaths despite the emergence of highly transmissible variants.
Phylogenomic evidence for the Origin of Obligately Anaerobic Anammox Bacteria around the Great Oxidation Event
Authors: Liao Tianhua , Wang Sishuo , Stüeken Eva E. , Luo Haiwei
Published: July 2021

The anaerobic ammonium oxidation (anammox) bacteria could transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remains enigmatic. Here, we performed comprehensive phylogenomic analysis and showed a single origin of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which includes implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based approach, we estimated that anammox bacteria originated at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32 to 2.5 billion years ago [Ga]) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress, bioenergetics and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria.
The role of posterior ventral stream areas for viewpoint-invariant object recognition
Authors: Nestmann Sophia , Karnath Hans-Otto , Rennig Johannes
Published: July 2021

Object constancy is one of the most crucial mechanisms of the human visual system enabling viewpoint invariant object recognition. However, the neuronal foundations of object constancy are widely unknown. Research has shown that the ventral visual stream is involved in processing of various kinds of object stimuli and that several regions along the ventral stream are possibly sensitive to the orientation of an object in space. To systematically address the question of viewpoint sensitive object perception, we conducted a study with stroke patients as well as an fMRI experiment with healthy participants applying object stimuli in several spatial orientations, for example in typical and atypical viewing conditions. In the fMRI experiment, we found stronger BOLD signals and above-chance classification accuracies for objects presented in atypical viewing conditions in fusiform face sensitive and lateral occipito-temporal object preferring areas. In the behavioral patient study, we observed that lesions of the right fusiform gyrus were associated with lower performance in object recognition for atypical views. The complementary results from both experiments emphasize the contributions of fusiform and lateral-occipital areas to visual object constancy and indicate that visual object constancy is particularly enabled through increased neuronal activity and specific activation patterns for objects in demanding viewing conditions.
A behavioral architecture for realistic simulations ofDrosophilalarva locomotion and foraging
Authors: Sakagiannis Panagiotis , Jürgensen Anna-Maria , Nawrot Martin Paul
Published: July 2021

TheDrosophilalarva is extensively used as model organism in neuroethological studies where precise behavioral tracking enables the statistical analysis of individual and population-level behavioral metrics that can inform mathematical models of larval behavior. Here, we propose a hierarchical model architecture comprising three layers to facilitate modular model construction, closed-loop simulations, and direct comparisons between empirical and simulated data. At the basic layer, the autonomous locomotory model is capable of performing exploration. Based on novel kinematic analyses our model features intermittent forward crawling that is phasically coupled to lateral bending. At the second layer, navigation is achieved via active sensing in a simulated environment and top-down modulation of locomotion. At the top layer, behavioral adaptation entails associative learning. We evaluate virtual larval behavior across agent-based simulations of autonomous free exploration, chemotaxis, and odor preference testing. Our behavioral architecture is ideally suited for the modular combination of neuromechanical, neural or mere statistical model components, facilitating their evaluation, comparison, extension and integration into multifunctional control architectures.
Inhibition of cholinergic interneurons potentiates corticostriatal transmission in D1 receptor-expressing medium-sized spiny neurons and restores motor learning in parkinsonian condition
Authors: Laverne Gwenaelle , Pesce Jonathan , Reynders Ana , Melon Christophe , Goff Lydia Kerkerian-Le , Maurice Nicolas , Beurrier Corinne
Published: July 2021

Striatal cholinergic interneurons (CINs) respond to salient or reward prediction-related stimuli after conditioning with brief pauses in their activity, implicating them in learning and action selection. This pause is lost in animal models of Parkinson’s disease. How this signal regulates the functioning of the striatum remains an open question. To address this issue, we examined the impact of CIN firing inhibition on glutamatergic transmission between the cortex and the medium-sized spiny projection neurons expressing dopamine D1 receptors (D1 MSNs). Brief interruption of CIN activity had no effect in control condition whereas it increased glutamatergic responses in D1 MSNs after nigrostriatal dopamine denervation. This potentiation was dependent upon M4 muscarinic receptor and protein kinase A. Decreasing CIN firing by opto/chemogenetic strategies in vivo rescued long-term potentiation in some MSNs and alleviated motor learning deficits in parkinsonian mice. Taken together, our findings demonstrate that the control exerted by CINs on corticostriatal transmission and striatal-dependent motor-skill learning depends on the integrity of dopaminergic inputs.
Motion/direction-sensitive thalamic neurons project extensively to the middle layers of primary visual cortex
Authors: Zhuang Jun , Wang Yun , Ouellette Naveen D. , Turschak Emily , Larsen Rylan S. , Takasaki Kevin T. , Daigle Tanya L. , Tasic Bosiljka , Waters Jack , Zeng Hongkui , Reid R. Clay
Published: July 2021

The motion/direction-sensitive and location-sensitive neurons are two major functional types in mouse visual thalamus that project to the primary visual cortex (V1). It has been proposed that the motion/direction-sensitive neurons mainly target the superficial layers in V1, in contrast to the location-sensitive neurons which mainly target the middle layers. Here, by imaging calcium activities of motion/direction-sensitive and location-sensitive axons in V1, we find no evidence for these cell-type specific laminar biases at population level. Furthermore, using a novel approach to reconstruct single-axon structures with identified in vivo response types, we show that, at single-axon level, the motion/direction-sensitive axons have middle layer preferences and project more densely to the middle layers than the location-sensitive axons. Overall, our results demonstrate that Motion/direction-sensitive thalamic neurons project extensively to the middle layers of V1, challenging the current view of the thalamocortical organizations in the mouse visual system.
Reflective mirror-based line-scan adaptive optics OCT
Authors: Pandiyan Vimal Prabhu , Jiang Xiaoyun , Kuchenbecker James A. , Sabesan Ramkumar
Published: July 2021

Line-scan OCT, incorporated with adaptive optics (AO), offers high resolution, speed and sensitivity for imaging retinal structure and function in vivo. Here, we introduce its implementation with reflective mirror-based afocal telescopes, optimized for imaging light-induced retinal activity (optoretinography) and weak retinal reflections at the cellular scale. A non-planar optical design was followed based on previous recommendations with key differences specific to a line-scan geometry. The three beam paths fundamental to an OCT system – illumination/sample, detection, and reference – were modeled in Zemax optical design software to yield theoretically diffraction-limited performance over a 2.2 deg. field-of-view and 1.5 D vergence range at the eye’s pupil. The performance for imaging retinal structure was exemplified by cellular-scale visualization of retinal ganglion cells, macrophages, foveal cones, and rods in human observers. The performance for functional imaging was exemplified by resolving the light-evoked optical changes in foveal cone photoreceptors where the spatial resolution was sufficient for cone spectral classification at an eccentricity 0.3 deg. from the foveal center. This enabled the first in vivo demonstration of reduced S-cone (short-wavelength cone) density in the human foveola, thus far observed only in ex vivo histological preparations. Together, the feasibility for high resolution imaging of retinal structure and function demonstrated here holds significant potential for basic science and translational applications.