bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and outcomes of SARS-COV 2 critically ill patients after emergence of the variant of concern 20H/501Y.V2: A comparative cohort study
Authors: Aries Philippe , Huet Olivier , Balicchi Julien , Mathais Quentin , Estagnasie Camille , Martin-Lecamp Gonzague , Simon Olivier , Morvan Anne-Cécile , Puech Bérénice , Subiros Marion , Blonde Renaud , Boue Yvonnick
Published: September 2022

There are currently no data regarding characteristics of critically ill patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant of concern (VOC) 20H/501Y.V2. We therefore aimed to describe changes of characteristics in critically ill patients with Covid-19 between the first and the second wave when viral genome sequencing indicated that VOC was largely dominant in Mayotte Island (Indian Ocean). Consecutive patients with Covid-19 and over 18 years admitted in the unique intensive care unit (ICU) of Mayotte during wave 2 were compared with an historical cohort of patients admitted during wave 1. We performed a LR comparing wave 1 and wave 2 as outcomes. To complete analysis, we built a Random Forest model (RF), that is, a machine learning classification tool- using the same variable set as that of the LR. We included 156 patients, 41 (26.3%) and 115 (73.7%) belonging to the first and second waves respectively. Univariate analysis did not find difference in demographic data or in mortality. Our multivariate LR found that patients in wave 2 had less fever (absence of fever aOR 5.23, 95% confidence interval (CI) 1.89–14.48, p = .001) and a lower simplified acute physiology score (SAPS II) (aOR 0.95, 95% CI 0.91–0.99, p = .007) at admission; at 24 hours, the need of invasive mechanical ventilation was higher (aOR 3.49, 95% CI 0.98–12.51, p = .055) and pO2/FiO2 ratio was lower (aOR 0.99, 95 % CI 0.98–0.99, p = .03). Patients in wave 2 had also an increased risk of ventilator-associated pneumonia (VAP) (aOR 4.64, 95% CI 1.54–13.93, p = .006). Occurrence of VAP was also a key variable to classify patients between wave 1 and wave 2 in the variable importance plot of the RF model. Our data suggested that VOC 20H/501Y.V2 could be associated with a higher severity of respiratory failure at admission and a higher risk for developing VAP. We hypothesized that the expected gain in survival brought by recent improvements in critical care management could have been mitigated by increased transmissibility of the new lineage leading to admission of more severe patients. The immunological role of VOC 20H/501Y.V2 in the propensity for VAP requires further investigations.
Predictors of survival for pediatric extracorporeal cardiopulmonary resuscitation: A systematic review and meta-analysis
Authors: Sood Nitish , Sangari Anish , Goyal Arnav , Conway J. Arden S.
Published: September 2022

Background:

The use of extracorporeal cardiopulmonary resuscitation (ECPR) has improved survival in patients with cardiac arrest; however, factors predicting survival remain poorly characterized. A systematic review and meta-analysis was conducted to examine the predictors of survival of ECPR in pediatric patients.

Methods:

We searched EMBASE, PubMed, SCOPUS, and the Cochrane Library from 2010 to 2021 for pediatric ECPR studies comparing survivors and non-survivors. Thirty outcomes were analyzed and classified into 5 categories: demographics, pre-ECPR laboratory measurements, pre-ECPR co-morbidities, intra-ECPR characteristics, and post-ECPR complications.

Results:

Thirty studies (n = 3794) were included. Pooled survival to hospital discharge (SHD) was 44% (95% CI: 40%–47%, I
2 = 67%). Significant predictors of survival for pediatric ECPR include the pre-ECPR lab measurements of PaO2, pH, lactate, PaCO2, and creatinine, pre-ECPR comorbidities of single ventricle (SV) physiology, renal failure, sepsis, ECPR characteristics of extracorporeal membrane oxygenation (ECMO) duration, ECMO flow rate at 24 hours, cardiopulmonary resuscitation (CPR) duration, shockable rhythm, intra-ECPR neurological complications, and post-ECPR complications of pulmonary hemorrhage, renal failure, and sepsis.

Conclusion:

Prior to ECPR initiation, increased CPR duration and lactate levels had among the highest associations with mortality, followed by pH. After ECPR initiation, pulmonary hemorrhage and neurological complications were most predictive for survival. Clinicians should focus on these factors to better inform potential prognosis of patients, advise appropriate patient selection, and improve ECPR program effectiveness.
Sugammadex for reversing neuromuscular blockages after lung surgery: A systematic review and meta-analysis
Authors: Yang Jia-Li , Chen Kuen-Bao , Shen Mei-Ling , Hsu Wei-Ti , Lai Yu-Wen , Hsu Chieh-Min
Published: September 2022

Background:

This study determined whether sugammadex was associated with a lower risk of postoperative pulmonary complications and improved outcomes in lung surgeries.

Methods:

A systematic literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library from January 2000 to March 2022. The characteristics of lung surgeries using sugammadex treatment compared with control drugs and postoperative outcomes were retrieved. The primary outcome was estimated through a pooled odds ratio (OR) and its 95% confidence interval (CI) was identified using a random-effects model.

Results:

From 465 citations, 7 studies with 453 patients receiving sugammadex and 452 patients receiving a control were included. The risk of postoperative pulmonary complication (PPCs) was lower in the sugammadex group than in the control group. Also, it showed that the effect of sugammadex on PPCs in the subgroup analysis was significantly assessed on the basis of atelectasis or non-atelectasis. Furthermore, subgroup analysis based on the relationship between high body mass index (BMI) and PPCs also showed that sugammadex had less occurrence in both the high BMI (defined as BMI ≥ 25) and low BMI groups. No difference in length of hospital stay (LOS) between the two groups was observed.

Conclusion:

This study observed that although reversing neuromuscular blockages with sugammadex in patients undergoing thoracic surgery recorded fewer PPCs and shorter extubation periods than conventional reversal agents, no difference in LOS, postanaesthesia care unit (PACU) stay length and chest tube insertion duration in both groups was observed.
Plasma and vitreous selenium concentrations in patients with type 2 diabetes and diabetic retinopathy
Authors: Wang Chunmiao , Ran Ruijin , Jin Xin , Zhu Xiaohong
Published: September 2022

Background:

This work aimed to determine and compare plasma and vitreous selenium (Se) concentrations in patients with type 2 diabetes and diabetic retinopathy (DR).

Methods:

A total of 60 type-2-diabetes patients including 20 without DR, 20 with non-proliferative DR (NPDR), and 20 with proliferative diabetic retinopathy (PDR), were involved in this study. Blood plasma samples were collected from above 60 patients and 20 normal controls (without diabetes). Twenty control vitreous samples were obtained from the eyes presenting a macular hole and epimacular membrane. Vitreous samples were also collected from PDR patients receiving one-week intravitreal anti-VEGF therapy or not. Plasma and vitreous Se concentrations were determined by inductively coupled plasma mass spectrometry.

Results:

Plasma Se concentrations in PDR patients (163.74 ± 32.68 μg/L) were significantly higher than those in normal control patients (121.59 ± 28.33 μg/L), NPDR patients (130.34 ± 29.11 μg/L), and the patients without DR (81.23 ± 20.59 μg/L) (all P < .001). Similarly, Se concentrations in vitreous samples of PDR patients (56.30 ± 12.03 μg/L) were consistently higher than those in control vitreous samples (26.26 ± 6.53 μg/L). In addition, vitreous Se concentrations in PDR patients decreased to 47.76 ± 9.72 μg/L after intravitreal injection of the anti-VEGF drug ranibizumab for one week, which was significantly lower than those before injection (P = .02). Plasma VEGF levels of diabetic patients were lower than those of the normal controls (P < .001). On the contrary, the vitreous VEGF level in the PDR group (913.61 ± 193.32 pg/mL) was significantly higher than that of the normal control group (101.23 ± 21.33 pg/mL) (P < .001).

Conclusion:

The elevation of Se concentrations may be an important risk factor in plasma and vitreous with diabetic retinopathy among type-2-diabetes patients. The elevated VEGF may be also closely related to the intraocular Se concentration in PDR patients.
Comparison of high flow oxygen therapy versus noninvasive mechanical ventilation for successful weaning from invasive ventilation in children: An observational study
Authors: Celik Nur Berna , Tanyildiz Murat , Yetimakman Filiz , Kesici Selman , Bayrakci Benan
Published: September 2022

Post-extubation respiratory failure is associated with a poor prognosis due to increased ventilator-associated pneumonia, and longer length of stay in the ICU and hospital. In this study, we aimed to evaluate the efficacy of high-flow nasal cannula (HFNC) and noninvasive mechanical ventilation (NIMV) on extubation success in children. A total of 48 patients, aged between 1 month and 18 years, who were weaned to either NIMV or HFNC were included. Patients who had tracheostomy or were not weaned and underwent unplanned extubation were excluded. Age, gender, anthropometric parameters, Pediatric Risk of Mortality and Pediatric Logistic Organ Dysfunction scores, oxygenation index, mechanical ventilation length of stay (LOS), HFNC/NIMV LOS, Modified Downes-Silverman score (MDS), and venous blood gas parameters, pediatric intensive care unit (PICU) LOS were recorded. 24 patients were extubated to NIMV, and 24 patients to HFNC. HFNC LOS and NIMV LOS were similar (P = .621). The failure rates at the 48th hour of HFNC and NIMV were 33% (n = 8), and 33% respectively (n = 8) (P = 1.0). PICU LOS and mortality rate was also similar (P = .06, P = .312 respectively). MDS decreased significantly in both groups (P < .001, P = .02 respectively). Changes in blood gas parameters and MDS within the first 48-hour of device application were similar between the 2 groups. HFNC is not inferior to NIMV in patients with extubation difficulty or those expected to have such difficulty in terms of treatment success, PICU LOS, and mortality. Therefore, HFNC appears to be a weaning technique alternative to NIMV after extubation.
Floating-dislocated elbow in adults: Case reports and literature review
Authors: Veliceasa Bogdan , Pertea Mihaela , Popescu Dragos , Carp Claudiu Adrian , Pinzaru Roxana , Huzum Bogdan , Alexa Ovidiu , Strobescu-Ciobanu Cristina , Filip Alexandru
Published: September 2022

Rationale:

Floating-dislocated elbow is a severe and extremely rare injury in adults. Reviewing the literature, we found around 6 case reports regarding floating-dislocated elbow in adults.

Patient concerns and diagnoses:

We report 2 cases of this unusual injury association. Both patients suffered a high energy trauma – fall from a height. Initial X-rays (radiography) revealed in both cases the fractures above and below the elbow (floating elbow) and associated elbow dislocation (floating-dislocated elbow). One case was a type IIIB Gustilo-Anderson open fracture-dislocation with an intra-articular component (olecranon fracture).

Interventions and outcomes:

Each case had his own management problem regarding what to treat first: the dislocation or the associated fractures? Fractures were treated surgically by reduction and internal fixation, and after elbow dislocation reduction, the upper limb was immobilized in a long, well-padded plaster, with the elbow in 90° of flexion, for 3 weeks. Bone union was observed radiographically at 2 months after surgery in both cases. At the 2-year follow-up we recorded full upper limb recovery in terms of muscular trophism and elbow full range of motion.

Lessons:

In addition to adding 2 new cases to a lower number of such lesion associations in adults, we also added a new variant of floating-dislocated elbow which has not been reported until now in the literature. Prompt management of these injuries, with stable fixation of the fractures allowed for early rehabilitation with excellent 2-years functional outcome.
Arthroscopic cartilage regeneration facilitating procedure: A decompressing arthroplasty for knee osteoarthritis
Authors: Lyu Shaw-Ruey , Hsu Chia-Chen , Hung Jung-Pin , Chou Li-Chan , Chen Yu-Ruei , Lin Chih-Wen
Published: September 2022

The effectiveness of arthroscopic treatment for knee osteoarthritis (OA) has always been a subject of debate. This study presents an innovative concept for the arthroscopic management of knee OA and investigates its clinical outcomes. An arthroscopic cartilage regeneration facilitating procedure (ACRFP) was performed on 693 knees of 411 patients with knee OA, with a mean age of 60 years (34–90 years), to eliminate the medial abrasion phenomenon (MAP) and decompress the patellofemoral joints. The Knee Society Score (KSS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) were used to determine the subjective outcome. Roentgenographic changes in all cases and magnetic resonance imaging (MRI) variations in 20 randomly selected cases were evaluated for objective outcomes. We evaluated 634 knees in 369 patients (93.7%) with more than 3 years of follow-up (mean, 40 months; SD, 9) and found that the overall subjective satisfaction rate was 91.1%. Scores for KSS and all KOOS subscales improved statistically. Reversal of cartilage degeneration was observed in 80.1% of the entire series (radiographic outcome study) and 72.2% of the 18 randomly selected cases (1-year MRI outcome study). We found significant association between gender and OA severity, with regards to the subjective outcomes. Age, body mass index, pre-operative hyaluronic acid injection, OA severity, and type and severity of the medial plica were found to be important predictors of radiographic outcomes. An analysis of failed cases reaffirmed the need for early ACRFP and skilled post-operative care. ACRFP is an effective treatment for knee OA. It can benefit most patients and modify their degeneration processes if performed in time. However, further investigations are needed to confirm our concept of treatment.
Mortality prediction upon hospital admission – the value of clinical assessment: A retrospective, matched cohort study
Authors: Glick Noam , Vaisman Adva , Negru Liat , Segal Gad , Itelman Eduard
Published: September 2022

Accurate prediction of mortality upon hospital admission is of great value, both for the sake of patients and appropriate resources’ allocation. A myriad of assessment tools exists for this purpose. The evidence relating to the comparative value of clinical assessment versus established indexes are scarce. We analyzed the accuracy of a senior physician’s clinical assessment in a retrospective cohort of patients in a crude, general patients’ population and later on a propensity matched patients’ population. In one department of internal medicine in a tertiary hospital, of 9891 admitted patients, 973 (10%) were categorized as prone to death in a 6-months’ duration by a senior physician. The risk of death was significantly higher for these patients [73.1% vs 14.1% mortality within 180 days; hazard ratio (HR) = 7.58; confidence intervals (CI) 7.02‐8.19, P < .001]. After accounting for multiple, other patients’ variables associated with increased risk of mortality, the correlation remained significant (HR = 3.25; CI 2.85‐3.71, P < .001). We further performed a propensity matching analysis (a subgroup of 710 patients, subdivided to two groups with 355 patients each): survival rates were as low as 45% for patients categorized as prone to death compared to 78% in patients who weren’t categorized as such (P < .001). Reliance on clinical evaluation, done by an experienced senior physician, is an appropriate tool for mortality prediction upon hospital admission, achieving high accuracy rates.
An Overview of Mindfulness-Oriented Addiction and Pain Recovery
Authors: Biedlingmaier Andrew J. , Yovankin Timothy G. , Koola Maju Mathew , Yanuck Michael , Varghese Sajoy Purathumuriyil
Published: September 2022

There is evidence that mindfulness-based interventions are effective as stress-reduction techniques in people with various stressor-related disorders. Research also shows overall improvement in mental health well-being in practitioners of mindfulness. However, there is limited literature probing the potential negative impacts of mindfulness practice. Relapse is a major challenge in substance use disorders (SUDs), particularly for people with chronic pain. There is an overlap between SUDs and chronic pain, which share common pathophysiological pathways that could contribute to poor pain control and mental instability. In this report, we discuss the possible effects of mindfulness on specified aspects of substance craving and chronic pain perception. We propose future directions for research in mindfulness practices to maximize the potential for relapse prevention and pain control.
Prolonged Impact of COVID-19 on Job Prospects and Training for Pediatric Gastroenterology Fellows in North America
Authors: Sanchez Raul E. , Grossman Arielle , Irastorza Laura E. , Mallon Daniel , Lee Christine K.
Published: September 2022

Objectives:

As the COVID-19 pandemic persisted into the 2020 to 2021 academic year, there was a continued effect on graduate medical education trainees and graduating trainee job attainment. Our survey aims to investigate how the pandemic has continued to affect job search and attainment for pediatric gastroenterology fellows as well as to re-evaluate the pandemic’s impact on pediatric gastroenterology fellow educational experiences.

Methods:

An anonymous survey was distributed to all North American pediatric gastroenterology fellows from May to June 2021. Survey questions included topics related to job search and fellowship training and were tailored to respondent year of training.

Results:

Of 453 pediatric gastroenterology fellows in the 2020 to 2021 academic year, 158 fellows (35%) responded to the survey. Of graduating fellow respondents with job contracts, 74% reported willingness to make compromises in their job search, 76% reported accepting academic positions that were primary clinical, and 42% estimated staying at their accepted job for less than 5 years. When asked about the impact of COVID-19 on various aspects of fellowship education, a negative impact was reported in the following areas: 76% in research, 94% in clinical experience, 73% in procedural skills, and 84% in didactics.

Conclusion:

The COVID-19 pandemic continues to make a significant impact on pediatric gastroenterology fellowship education and the job attainment process. Regarding accepted job positions, we found substantial willingness to compromise, a shorter duration to stay at the job than expected, and minimal research focus. This raises concern regarding job preparedness and satisfaction as fellows complete their medical training.
Stem Cells in Temporomandibular Joint Engineering: State of Art and Future Persectives
Authors: Minervini Giuseppe , Del Mondo Daniela , Russo Diana , Cervino Gabriele , D’Amico Cesare , Fiorillo Luca
Published: September 2022

Temporomandibular joint (TMJ) osteoarthritis is a degenerative disease, characterized by gradual cartilage degradation, bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical therapy have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In last years, stem cell-based therapy has collected much attention as a possible approach toward tissue repair and regeneration. Mesenchymal stem cells (MSCs), derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will describe the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ, particularly focusing on the MSC-based therapy and tissue engineering.
Consciousness as a Memory System
Authors: Budson Andrew E. , Richman Kenneth A. , Kensinger Elizabeth A.
Published: September 2022

We suggest that there is confusion between why consciousness developed and what additional functions, through continued evolution, it has co-opted. Consider episodic memory. If we believe that episodic memory evolved solely to accurately represent past events, it seems like a terrible system—prone to forgetting and false memories. However, if we believe that episodic memory developed to flexibly and creatively combine and rearrange memories of prior events in order to plan for the future, then it is quite a good system. We argue that consciousness originally developed as part of the episodic memory system—quite likely the part needed to accomplish that flexible recombining of information. We posit further that consciousness was subsequently co-opted to produce other functions that are not directly relevant to memory per se, such as problem-solving, abstract thinking, and language. We suggest that this theory is compatible with many phenomena, such as the slow speed and the after-the-fact order of consciousness, that cannot be explained well by other theories. We believe that our theory may have profound implications for understanding intentional action and consciousness in general. Moreover, we suggest that episodic memory and its associated memory systems of sensory, working, and semantic memory as a whole ought to be considered together as the conscious memory system in that they, together, give rise to the phenomenon of consciousness. Lastly, we suggest that the cerebral cortex is the part of the brain that makes consciousness possible, and that every cortical region contributes to this conscious memory system.
Vitamin B12 biosynthesis of Cetobacterium ceti isolated from the intestinal content of captive common bottlenose dolphins (Tursiops truncatus)
Authors: Suzuki Akihiko , Shirakata Chika , Anzai Hiroshi , Sumiyama Daisuke , Suzuki Miwa
Published: September 2022

In comparison with terrestrial mammals, dolphins require a large amount of haemoglobin in blood and myoglobin in muscle to prolong their diving time underwater and increase the depth they can dive. The genusCetobacteriumis a common gastrointestinal bacterium in dolphins and includes two species:C. someraeandC. ceti. Whilst the former produces vitamin B12, which is essential for the biosynthesis of haem, a component of haemoglobin and myoglobin, but not produced by mammals, the production ability of the latter remains unknown. The present study aimed to isolateC. cetifrom dolphins and reveal its ability to biosynthesize vitamin B12. Three strains ofC. ceti, identified by phylogenetic analyses with 16S rRNA gene and genome-based taxonomy assignment and biochemical features, were isolated from faecal samples collected from two captive common bottlenose dolphins (Tursiops truncatus). A microbioassay usingLactobacillus leichmanniiATCC 7830 showed that the average concentration of vitamin B12produced by the three strains was 11 (standard deviation: 2) pg ml−1. The biosynthesis pathway of vitamin B12, in particular, adenosylcobalamin, was detected in the draft genome of the three strains using blastKOALA. This is the first study to isolateC. cetifrom common bottlenose dolphins and reveal its ability of vitamin B12biosynthesis, and our findings emphasize the importance ofC. cetiin supplying haemoglobin and myoglobin to dolphins.
The Selection Landscape and Genetic Legacy of Ancient Eurasians
Authors: Irving-Pease Evan K. , Refoyo-Martínez Alba , Ingason Andrés , Pearson Alice , Fischer Anders , Barrie William , Sjögren Karl-Göran , Halgren Alma S. , Macleod Ruairidh , Demeter Fabrice , Henriksen Rasmus A. , Vimala Tharsika , McColl Hugh , Vaughn Andrew , Stern Aaron J. , Speidel Leo , Scorrano Gabriele , Ramsøe Abigail , Schork Andrew J. , Rosengren Anders , Zhao Lei , Kristiansen Kristian , Sudmant Peter H. , Lawson Daniel J. , Durbin Richard , Korneliussen Thorfinn , Werge Thomas , Allentoft Morten E. , Sikora Martin , Nielsen Rasmus , Racimo Fernando , Willerslev Eske
Published: September 2022

The Eurasian Holocene (beginning c. 12 thousand years ago) encompassed some
of the most significant changes in human evolution, with far-reaching
consequences for the dietary, physical and mental health of present-day
populations. Using an imputed dataset of >1600 complete ancient genome
sequences, and new computational methods for locating selection in time and
space, we reconstructed the selection landscape of the transition from hunting
and gathering, to farming and pastoralism across West Eurasia. We identify major
selection signals related to metabolism, possibly associated with the dietary
shift occurring in this period. We show that the selection on loci such as the
FADS cluster, associated with fatty acid metabolism, and the lactase persistence
locus, began earlier than previously thought. A substantial amount of selection
is also found in the HLA region and other loci associated with immunity,
possibly due to the increased exposure to pathogens during the Neolithic, which
may explain the current high prevalence of auto-immune disease, such as
psoriasis, due to genetic trade-offs. By using ancient populations to infer
local ancestry tracks in hundreds of thousands of samples from the UK Biobank,
we find strong genetic differentiation among ancient Europeans in loci
associated with anthropometric traits and susceptibility to several diseases
that contribute to present-day disease burden. These were previously thought to
be caused by local selection, but in fact can be attributed to differential
genetic contributions from various source populations that are ancestral to
present-day Europeans. Thus, alleles associated with increased height seem to
have increased in frequency following the Yamnaya migration into northwestern
Europe around 5,000 years ago. Alleles associated with increased risk of some
mood-related phenotypes are overrepresented in the farmer ancestry component
entering Europe from Anatolia around 11,000 years ago, while western
hunter-gatherers show a strikingly high contribution of alleles conferring risk
of traits related to diabetes. Our results paint a picture of the combined
contributions of migration and selection in shaping the phenotypic landscape of
present-day Europeans that suggests a combination of ancient selection and
migration, rather than recent local selection, is the primary driver of
present-day phenotypic differences in Europe.
Effectiveness and mechanisms of a multimodal treatment for low back pain: a pragmatic matched cohort study
Authors: Schäfer Robin , Niederer Daniel , Levenig Claudia , Hasenbring Monika , Tas Thomas , Fett Daniela , Trompeter Katharina , Haag Thore , Schneider Christian , Floessel Philipp , Beck Heidrun , Schiltenwolf Marcus , Wippert Pia-Maria , Engel Tilman , Mayer Frank , Platen Petra
Published: September 2022

Objective

To investigate the effectiveness and mechanisms of a multimodal treatment including perturbation exercise.

Methods

A matched cohort study was conducted. The intervention consists of a 12-week back pain prevention course with perturbation exercise and education embedded in primary health care according to German social law. Participants from the intervention group had chronic or recurrent low back pain with heterogenous but on average rather low pain and chronification. Control groups (usual care) were matched from a multi-center RCT. Outcomes were pain, disability, isokinetic trunk strength and balance. Bayesian regression models were used to estimate the Average Treatment effect on the Treated (ATT). Further, sub-group and mediation analyses within the intervention group using the biopsychological avoidance-endurance model were conducted. Median values with highest posterior density intervals (HPDI) from baseline-adjusted analyses are presented.

Results

Over 12 weeks, intervention and control (n = 128 each) experienced a similar decrease in pain and disability, which led to negligible ATTs for pain (−0.3 (HPDI95% [-4.3, 3.4]) and disability (−0.2 (HPDI95% [-4, 3.7])). Changes in functional parameters (n=18) showed small effects in favor of the intervention group, in particular for monopedal stances (standardized mean difference: -0.5 HPDI95% [-0.79, -0.21]). Depression was higher in drop-outs and decreases in pain/disability were associated with decreases in depression. Distress-endurance subgroups experienced higher baseline pain and disability and showed the highest reductions in both parameters upon completion of the intervention.

Conclusion

Perturbation exercise with education yielded only small treatment effects in a heterogenous population with rather mild symptoms. Targeting distress-endurance subgroups with a multimodal treatment approach is probably an effective strategy in treatment tailoring.
Covid-19: Qualitative Change in the Behavior of the “Virus vs Human” System - From Limit Cycle to Sustained Focus
Authors: Sokolov Alexander V.
Published: September 2022

Annotation

The high contagiousness of the latest strains of Covid-19 qualitatively changes the behavior of the “virus vs human” system. Numerical experiments with a model of the Covid-19 epidemic in Moscow have shown that a reproduction number R0 of about 4 is critical, defining a qualitative change in the dynamics of the epidemic. Below this value (observed until 2022), the long-term forecast tends to undamped oscillations; above this value, it is described by damped oscillations: amplitudes of the epidemic waves get smaller and smaller, with a constant, very high background level of morbidity (or high-intensity vaccination) that maintains the state of natural immunity at a level close to 100% (reaching 93.7% for the current R0 value of about 16). At the limit, the system tends to a stable equilibrium point. Here we consider a reduced model of epidemic dynamics. Its study (search for equilibrium solutions, analysis of their stability, construction a bifurcation diagram and a phase portrait) confirms the presence of points of qualitative change in the behavior of the “virus vs human” system (bifurcation points). Some practical results for Moscow are given. A further increase in the contagiousness of the virus does not change the picture significantly, thus more infectious strains are not to be feared. The key parameter of the study is the function of the immunity level depending on the time after the disease. The damping of omicron waves (oscillations), observed recently in many countries, is a confirmation of the correctness of the accepted hypotheses.
Accurate Bayesian segmentation of thalamic nuclei using diffusion MRI and an improved histological atlas
Authors: Tregidgo Henry F. J. , Soskic Sonja , Althonayan Juri , Maffei Chiara , Van Leemput Koen , Golland Polina , Yendiki Anastasia , Alexander Daniel C. , Bocchetta Martina , Rohrer Jonathan D. , Iglesias Juan Eugenio ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2022

The human thalamus is a highly connected brain structure, which is key for the control of numerous functions and is involved in several neurological disorders. Recently, neuroimaging studies have increasingly focused on the volume and connectivity of the specific nuclei comprising this structure, rather than looking at the thalamus as a whole. However, accurate identification of cytoarchitectonically designed histological nuclei on standard in vivo structural MRI is hampered by the lack of image contrast that can be used to distinguish nuclei from each other and from surrounding white matter tracts. While diffusion MRI may offer such contrast, it has lower resolution and lacks some boundaries visible in structural imaging. In this work, we present a Bayesian segmentation algorithm for the thalamus. This algorithm combines prior information from a probabilistic atlas with likelihood models for both structural and diffusion MRI, allowing label boundaries to be informed by both modalities. We present an improved probabilistic atlas, incorporating 26 thalamic nuclei identified from histology and 45 white matter tracts identified in ultra-high gradient strength diffusion imaging. We present a family of likelihood models for diffusion tensor imaging, ensuring compatibility with the vast majority of neuroimaging datasets that include diffusion MRI data. The use of these diffusion likelihood models greatly improves identification of nuclei versus segmentation based solely on structural MRI. Dice comparison of 5 manually identifiable groups of nuclei to ground truth segmentations show improvements of up to 10 percentage points. Additionally, our chosen model shows a high degree of reliability, with median test-retest Dice scores above 0.85 for four out of five nuclei groups, whilst also offering improved detection of differential thalamic involvement in Alzheimer’s disease (AUROC 83.36%). The probabilistic atlas and segmentation tool will be made publicly available as part of the neuroimaging package FreeSurfer.
Simultaneous Inference of Past Demography and Selection from the Ancestral Recombination Graph under the Beta Coalescent
Authors: Korfmann Kevin , Sellinger Thibaut , Freund Fabian , Fumagalli Matteo , Tellier Aurélien
Published: September 2022

The reproductive mechanism of a species is a key driver of genome evolution. The standard Wright-Fisher model for the reproduction of individuals in a population assumes that each individual produces a number of offspring negligible compared to the total population size. Yet many species of plants, invertebrates, prokaryotes or fish exhibit neutrally skewed offspring distribution or strong selection events yielding few individuals to produce a number of offspring of up to the same magnitude as the population size. As a result, the genealogy of a sample is characterized by multiple individuals (more than two) coalescing simultaneously to the same common ancestor. The current methods developed to detect such multiple merger events do not account for complex demographic scenarios or recombination, and require large sample sizes. We tackle these limitations by developing two novel and different approaches to infer multiple merger events from sequence data or the ancestral recombination graph (ARG): a sequentially Markovian coalescent (SMβC) and a graph neural network (GNNcoal). We first give proof of the accuracy of our methods to estimate the multiple merger parameter and past demographic history using simulated data under theβ-coalescent model. Secondly, we show that our approaches can also recover the effect of positive selective sweeps along the genome. Finally, we are able to distinguish skewed offspring distribution from selection while simultaneously inferring the past variation of population size. Our findings stress the aptitude of neural networks to leverage information from the ARG for inference but also the urgent need for more accurate ARG inference approaches.
Beyond the metropolis: Street tree densities and resident perceptions on ecosystem services in small urban centers in India
Authors: Anujan Krishna , Velho Nandini , Kuriakose Giby , P J Ebin , Pandi Vivek , Nagendra Harini
Published: September 2022

The role of urban street trees has been extensively studied in large metropolises, where they contribute significantly to faunal habitat, provide critical ecosystem services to residents and contribute to human well-being. On the other hand, rapidly urbanizing cities in India have been poorly studied, despite multiple types of irreplaceable losses related to tree cover. However, being early in their urbanization history, these centers also represent opportunity for urban sustainability with potentially high remnant vegetation and human-nature connections. While megacities in developed countries move towards biophilic urban planning and participatory decision making, basic information on tree communities and their perceived services is a bottleneck in achieving these goals in such small urban centers. We assessed the street tree community and resident perceptions of ecosystem service values in Kochi and Panjim, two coastal cities in India under rapid development, through a combination of field measurements (258 transects, 931 trees) and semi-structured interviews (497 individuals). We found that mean street tree density is low in both cities, especially so in Kochi, and corresponds to perceptions of recent change in tree cover (−28% in Kochi, −11% in Panjim). The street tree community in both cities were dominated by ornamental avenue trees such as Albizia saman and Peltophorum pterocarpum, but native coastal species like Cocos nucifera, Terminalia catappa and Thespesia populnea were also common. Despite recent urban growth, residents in both cities reported low value of trees for food, fodder and medicine, but high value for regulating services like shade and water. Moreover, we found strong evidence for aesthetic and cultural values of trees in both cities, including through qualitative interviews. Our study establishes critical baselines for biophilic planning in these small urban centers towards urban sustainability.
Type 1 interferon perturbates clonal competition by reshaping human blood development
Authors: Lama Chhiring , Isakov Danielle , Rosenberg Shira , Quijada-Álamo Miguel , Saurty-Seerunghen Mirca S. , Moein Sara , Abera Tsega-Ab , Sakaguchi Olivia , Totwani Mansi , Freed Grace , Poon Chi-Lam , Parghi Neelang , Kubas-Meyer Andrea , Xie Amy X. , Omar Mohamed , Choi Daniel , Castillo-Tokumori Franco , Abu-Zeinah Ghaith , Dillard Alicia , Omans Nathaniel D. , Dusaj Neville , Chamely Paulina , Mimitou Eleni , Smibert Peter , Kosiorek Heidi E. , Dueck Amylou C. , Weinberg Rona , Chaligne Ronan , Marcellino Bridget , Marchionni Luigi , Patel Sanjay , Simonson Paul , Landau Dan A. , Wagenblast Elvin , Hoffman Ronald , Nam Anna S.
Published: September 2022

Inflammation perturbs evolutionary dynamics of hematopoietic stem cell (HSC) clones in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasm (MPN) at baseline and following interferon-⍺ (IFN⍺) treatment, the only MPN therapy to deplete clonal stem cells. We focused on essential thrombocythemia, an informative model of early-phase neoplastic hematopoiesis. We integrated somatic genotyping, transcriptomes, immunophenotyping, and chromatin accessibility across single cells. IFN⍺ simultaneously activated HSCs into two polarized states, a lymphoid progenitor expansion associated with an anti-inflammatory state and an IFN⍺-specific inflammatory granulocytic progenitor (IGP) state derived directly from HSCs. The augmented lymphoid differentiation balanced the typical MPN-induced myeloid bias, associated with normalized blood counts. Clonal fitness upon IFN⍺ exposure was due to resistance of clonal stem cells to differentiate into IGPs. These results support a paradigm wherein inflammation perturbs clonal dynamics by HSC induction into the precipitous IGP differentiation program.

One-Sentence Summary

Inflammation accelerates clonal evolution by driving stem cell differentiation into an alternate interferon-⍺-induced progenitor state.
A global view of aging and Alzheimer’s pathogenesis-associated cell population dynamics and molecular signatures in the human and mouse brains
Authors: Sziraki Andras , Lu Ziyu , Lee Jasper , Banyai Gabor , Anderson Sonya , Abdulraouf Abdulraouf , Metzner Eli , Liao Andrew , Banfelder Jason , Epstein Alexander , Schaefer Chloe , Xu Zihan , Zhang Zehao , Gan Li , Nelson Peter T. , Zhou Wei , Cao Junyue
Published: September 2022

Conventional single-cell genomics approaches are limited by throughput and thus may have failed to capture aspects of the molecular signatures and dynamics of rare cell types associated with aging and diseases. Here, we developedEasySci, an extensively improved single-cell combinatorial indexing strategy, for investigating the age-dependent dynamics of transcription and chromatin accessibility across diverse brain cell types. We profiled ∼1.5 million single-cell transcriptomes and ∼400,000 single-cell chromatin accessibility profiles across mouse brains spanning different ages, genotypes, and both sexes. With a novel computational framework designed for characterizing cellular subtypes based on the expression of both genes and exons, we identified > 300 cell subtypes and deciphered their underlying molecular programs and spatial locations especially for rare cell types (e.g.,pinealocytes, tanycytes). Leveraging these data, we generated a global readout of age-dependent changes at cell subtype resolution, providing insights into cell types that expand (e.g.,rare astrocytes and vascular leptomeningeal cells in the olfactory bulb, reactive microglia, and oligodendrocytes) or are depleted (e.g.,neuronal progenitors, neuroblasts, committed oligodendrocyte precursors) as age progresses. Furthermore, we explored cell-type-specific responses to genetic perturbations associated with Alzheimer’s disease (AD) and identified rare cell types depleted (e.g., mt-Cytb+, mt-Rnr2+ choroid plexus epithelial cells) or enriched (e.g., Col25a1+,Ndrg1+ interbrain and midbrain neurons) in both AD models. Key findings are consistent between males and females, validated across the transcriptome, chromatin accessibility, and spatial analyses. Finally, we profiled a total of 118,240 single-nuclei transcriptomes from twenty-four post-mortem human brain samples derived from control and AD patients, revealing highly cell-type-specific and region-specific gene expression changes associated with AD pathogenesis. Critical AD-associated gene signatures were validated in both human and mice. In summary, these data comprise a rich resource for exploring cell-type-specific dynamics and the underlying molecular mechanisms in normal and pathological mammalian aging.
Selection and adaptive introgression guided the complex evolutionary history of the European common bean
Authors: Bellucci Elisa , Benazzo Andrea , Xu Chunming , Bitocchi Elena , Rodriguez Monica , Alseekh Saleh , Vittori Valerio Di , Gioia Tania , Neumann Kerstin , Cortinovis Gaia , Frascarelli Giulia , Murube Ester , Trucchi Emiliano , Nanni Laura , Ariani Andrea , Logozzo Giuseppina , Shin Jin Hee , Liu Chaochih , Jiang Liang , Ferreira Juan José , Campa Ana , Attene Giovanna , Morrell Peter Laurent , Bertorelle Giorgio , Graner Andreas , Gepts Paul , Fernie Alisdair Robert , Jackson Scott Allen , Papa Roberto
Published: September 2022

Domesticated crops have been disseminated by humans over vast geographic areas. After 1492, the common bean (Phaseolus vulgarisL.) was introduced in Europe. Here, we combine whole-genome profiling, metabolic fingerprinting and phenotypic characterisation, and we show that the first common bean cultigens successfully introduced into Europe were of Andean origin, after Francisco Pizarro’s expedition to northern Peru in 1529. We show that hybridisation, selection and recombination have shaped the genomic diversity of the European common bean in parallel with political constraints. There is clear evidence of adaptive introgression into the Mesoamerican-derived European genotypes, with 44 Andean introgressed genomic segments shared by more than 90% of European accessions and distributed across all chromosomes except PvChr11. Genomic scans for signatures of selection highlight the role of genes relevant to flowering and environmental adaptation, suggesting that introgression has been crucial for the dissemination of this tropical crop to the temperate regions of Europe.
Mass spectrometry of RNA-binding proteins during liquid-liquid phase separation reveals distinct assembly mechanisms and droplet architectures
Authors: Sahin Cagla , Motso Aikaterini , Gu Xinyu , Feyrer Hannes , Lama Dilraj , Arndt Tina , Rising Anna , Gese Genis Valentin , Hällberg Martin , Marklund Erik. G. , Schafer Nicholas P. , Petzold Katja , Teilum Kaare , Wolynes Peter G. , Landreh Michael
Published: September 2022

Phase separation of heterogeneous ribonucleoproteins (hRNPs) drives the formation of membraneless organelles, but structural information about their assembled states is still lacking. Here, we address this challenge through a combination of protein engineering, native ion mobility-mass spectrometry, and molecular dynamics simulations. We used a phase separation-compatible spider silk domain and pH changes to control the self-assembly of the hRNPs FUS, TDP-43, and hCPEB3, which are implicated in neurodegeneration, cancer, and memory storage. By releasing the proteins inside the mass spectrometer from their native assemblies, we could monitor conformational changes associated with phase separation. We find that NT*-FUS monomers undergo an unfolded-to-globular transition, whereas NT*-TDP-43 oligomerizes into partially disordered dimers and trimers. NT*-hCPEB3, on the other hand, remains fully disordered with a preference for fibrillar aggregation over phase separation. The divergent assembly mechanisms result in structurally distinct complexes, indicating differences in RNA processing and translation depending on biological context.
The small-bat-in-summer paradigm: energetics and adaptive behavioural routines of bats investigated through a stochastic dynamic model
Authors: Fjelldal Mari Aas , Muller Amandine Sophie , Ratikainen Irja Ida , Stawski Clare , Wright Jonathan
Published: September 2022

Strong seasonality at high latitudes represents a major challenge for many endotherms as they must balance survival and reproduction in an environment that varies widely in food availability and temperature. Being heterotherms, bats spend long cold winters in hibernation, avoiding the challenges faced by many animals. To avoid energetic mismatches caused by limited foraging time and stochastic weather conditions, bats can also employ this energy-saving state of torpor during summer to save accumulated energy reserves. However, at high latitudes small-bats-in-summer face a particular challenge: as nocturnal foragers they rely on the darkness of the night to avoid predators and/or interspecific competition, but for many the summer involves short nights of mostly twilight, and even a lack of true night at the northernmost distributions of some bat species. To investigate optimal individual behaviour across diurnal cycles, we constructed a stochastic dynamic model of bats living at high latitudes. Using a detailed parameterized model framework with values that are representative for our study system, we show that individual energetic reserves are a strong driver of day-time use of torpor and night-time foraging behaviour alike, with these linked effects being both temperature and photoperiod dependent. We further used the model framework to predict survival probabilities at five locations across a latitudinal gradient (60.1°N to 70.9°N), finding that photoperiod is the main limiting factor to bat species distributions. To verify the accuracy of our model results, we compared predictions for optimal decisions with our own empirical data collected on northern bats (Eptesicus nilssonii) from two latitudes in Norway. The similarities between our predictions and observations provide strong confirmation that this model framework incorporates the most important drivers of diurnal decision-making in bat physiology and behaviour. Our model findings regarding state-dependent decisions in bats should therefore contribute to the understanding of how bats cope with the summer challenges at high latitudes.