Draft genome sequences of two Micromonospora strains isolated from the root nodules of Alnus glutinosa.

In this paper, the draft genomes of Micromonospora RTGN7 and RTP1Z1, derived from Alnus glutinosa root nodules, are reported. The assembly of RTGN7 is 6.6 Mbp, composed of 59 contigs, with an N50 of 321,872. RTP1Z1's assembly is 6.3 Mbp, composed of 151 contigs, with an N50 of 76,442 bp.

Persistent complement dysregulation with signs of thromboinflammation in active Long Covid.

Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

Draft genome sequences of five Mycobacterium strains, isolated from Alnus glutinosa root nodules.

Mycobacterium is a clinically relevant genus of bacteria, with this paper reporting draft genomes of five Mycobacterium strains derived from Alnus glutinosa root nodules. The genome sizes of the isolates ranged from 6.1 to 6.9 Mbp, composed of 22-59 contigs. The N50 values ranged from 303,875 to 865,751 bp, presenting a GC% of 66.07%-66.96%.

Disentangling effects of remote mild traumatic brain injury characteristics and posttraumatic stress on processing speed and executive function in veterans.

Mild traumatic brain injury (mTBI) and posttraumatic stress are prevalent in military service members and share objective and subjective cognitive symptoms, complicating recovery. We investigated the effects of remote mTBI characteristics and current posttraumatic stress symptoms on neuropsychological performance in 152 veterans with a history of remote mTBI and current cognitive concerns. Participants completed clinical neuropsychological evaluations within a Veterans Affairs Level-II TBI/Polytrauma outpatient clinic (i.e. tertiary trauma care center for US military veterans outside of a research or teaching hospital setting). Archival data analysis of mTBI injury characteristics, clinical diagnoses, scores on the Posttraumatic Stress Disorder Checklist-Military Version (PCL-M) and performance on tests of processing speed, attention and executive function was conducted. Hierarchical linear regression demonstrated that elevated PCL-M scores were associated with slower performance on trail making test (TMT) Parts A and B (p < .016). PCL-M symptoms moderated the effect of alteration of consciousness (AOC) on TMT performance, with endorsement of AOC associated with better performance, but only when PCL-M scores were high (p < .005). Follow-up mediation analyses demonstrated that PCL-M score fully mediated the relationship between AOC and TMT-A performance and partially mediated the relationship between AOC and TMT-B performance. Post-hoc analyses meant to separate the impact of processing speed on TMT-B were all non-significant. Remote mTBI characteristics, specifically AOC, were not associated with decrements in cognitive performance. Posttraumatic symptoms were associated with worse processing speed, suggesting that psychological distress and psychopathology are contributing factors in understanding and treating persistent cognitive distress following remote mTBI.

Home Hospital Outcomes for Acute Decompensated Heart Failure and Factors Associated With Escalation of Care.

BACKGROUND: Overall outcomes and the escalation rate for home hospital admissions for heart failure (HF) are not known. We report overall outcomes, predict escalation, and describe care provided after escalation among patients admitted to home hospital for HF. METHODS: Our retrospective analysis included all patients admitted for HF to 2 home hospital programs in Massachusetts between February 2020 and October 2022. Escalation of care was defined as transfer to an inpatient hospital setting (emergency department, inpatient medical unit) for at least 1 overnight stay. Unexpected mortality was defined as mortality excluding those who desired to pass away at home on admission or transitioned to hospice. We performed the least absolute shrinkage and selection operator logistic regression to predict escalation. RESULTS: We included 437 hospitalizations; patients had a median age of 80 (interquartile range, 69-89) years, 58.1% were women, and 64.8% were White. Of the cohort, 29.2% had reduced ejection fraction, 50.9% had chronic kidney disease, and 60.6% had atrial fibrillation. Median admission Get With The Guidelines HF score was 39 (interquartile range, 35-45; 1%-5% predicted inpatient mortality). Escalation occurred in 10.3% of hospitalizations. Thirty-day readmission occurred in 15.1%, 90-day readmission occurred in 33.8%, and 6-month mortality occurred in 11.5%. There was no unexpected mortality during home hospitalization. Patients who experienced escalation had significantly longer median length of stays (19 versus 7.5 days, P<0.001). The most common reason for escalation was progressive renal dysfunction (36.2%). A low mean arterial pressure at the time of admission to home hospital was the most significant predictor of escalation in the least absolute shrinkage and selection operator regression. CONCLUSIONS: About 1 in 10 home hospital patients with HF required escalation; none had unexpected mortality. Patients requiring escalation had longer length of stays. A low mean arterial pressure at the time of admission to home hospital was the most important predictor of escalation of care in the least absolute shrinkage and selection operator logistic regression model.

Cost-effectiveness of Low-complexity Screening Tests in Community-based Case-finding for Tuberculosis.

INTRODUCTION: In high-burden settings, low-complexity screening tests for tuberculosis (TB) could expand the reach of community-based case-finding efforts. The potential costs and cost-effectiveness of approaches incorporating these tests are poorly understood. METHODS: We developed a microsimulation model assessing 3 approaches to community-based case-finding in hypothetical populations (India-, South Africa-, The Philippines-, Uganda-, and Vietnam-like settings) with TB prevalence 4 times that of national estimates: (1) screening with a point-of-care C-reactive protein (CRP) test, (2) screening with a more sensitive "Hypothetical Screening test" (95% sensitive for Xpert Ultra-positive TB, 70% specificity; equipment/labor costs similar to Xpert Ultra, but using a $2 cartridge) followed by sputum Xpert Ultra if positive, or (3) testing all individuals with sputum Xpert Ultra. Costs are expressed in 2023 US dollars and include treatment costs. RESULTS: Universal Xpert Ultra was estimated to cost a mean $4.0 million (95% uncertainty range: $3.5 to $4.6 million) and avert 3200 (2600 to 3900) TB-related disability-adjusted life years (DALYs) per 100 000 people screened ($670 [The Philippines] to $2000 [Vietnam] per DALY averted). CRP was projected to cost $550 (The Philippines) to $1500 (Vietnam) per DALY averted but with 44% fewer DALYs averted. The Hypothetical Screening test showed minimal benefit compared to universal Xpert Ultra, but if specificity were improved to 95% and per-test cost to $4.5 (all-inclusive), this strategy could cost $390 (The Philippines) to $940 (Vietnam) per DALY averted. CONCLUSIONS: Screening tests can meaningfully improve the cost-effectiveness of community-based case-finding for TB but only if they are sensitive, specific, and inexpensive.

Draft genome sequence of Streptomyces poriferorum RTGN2, a bacterial endophyte isolated from Alnus glutinosa root nodules.

Herein is reported the draft genome sequence of Streptomyces poriferum RTGN2, a bacterial isolate of Alnus glutinosa root nodules, collected from Saltwell Park, Gateshead, United Kingdom. The assembly is 9.5 Mbp in size, composed of 187 contigs, with a N50 of 189,630 bp, presenting a GC content of 71.2%.

Draft genome sequence of Amycolatopsis camponoti RTGN1, a bacterial endophyte isolated from Alnus glutinosa root nodules.

Here, we report the draft genome sequence of Amycolatopsis camponoti RTGN1, a bacterial endophyte of Alnus glutinosa root nodules, collected from Saltwell Park, United Kingdom. The genome is 11.9 Mbp in size, composed of 147 contigs, with an N50 of 179,211 bp and presenting a GC content of 70.9%.

Peripheral Transcriptomics in Acute and Long-Term Kidney Dysfunction in SARS-CoV2 Infection.

Background: Acute kidney injury (AKI) is common in hospitalized patients with SARS-CoV2 infection despite vaccination and leads to long-term kidney dysfunction. However, peripheral blood molecular signatures in AKI from COVID-19 and their association with long-term kidney dysfunction are yet unexplored. Methods: In patients hospitalized with SARS-CoV2, we performed bulk RNA sequencing using peripheral blood mononuclear cells(PBMCs). We applied linear models accounting for technical and biological variability on RNA-Seq data accounting for false discovery rate (FDR) and compared functional enrichment and pathway results to a historical sepsis-AKI cohort. Finally, we evaluated the association of these signatures with long-term trends in kidney function. Results: Of 283 patients, 106 had AKI. After adjustment for sex, age, mechanical ventilation, and chronic kidney disease (CKD), we identified 2635 significant differential gene expressions at FDR<0.05. Top canonical pathways were EIF2 signaling, oxidative phosphorylation, mTOR signaling, and Th17 signaling, indicating mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Comparison with sepsis associated AKI showed considerable overlap of key pathways (48.14%). Using follow-up estimated glomerular filtration rate (eGFR) measurements from 115 patients, we identified 164/2635 (6.2%) of the significantly differentiated genes associated with overall decrease in long-term kidney function. The strongest associations were 'autophagy', 'renal impairment via fibrosis', and 'cardiac structure and function'. Conclusions: We show that AKI in SARS-CoV2 is a multifactorial process with mitochondrial dysfunction driven by ER stress whereas long-term kidney function decline is associated with cardiac structure and function and immune dysregulation. Functional overlap with sepsis-AKI also highlights common signatures, indicating generalizability in therapeutic approaches. SIGNIFICANCE STATEMENT: Peripheral transcriptomic findings in acute and long-term kidney dysfunction after hospitalization for SARS-CoV2 infection are unclear. We evaluated peripheral blood molecular signatures in AKI from COVID-19 (COVID-AKI) and their association with long-term kidney dysfunction using the largest hospitalized cohort with transcriptomic data. Analysis of 283 hospitalized patients of whom 37% had AKI, highlighted the contribution of mitochondrial dysfunction driven by endoplasmic reticulum stress in the acute stages. Subsequently, long-term kidney function decline exhibits significant associations with markers of cardiac structure and function and immune mediated dysregulation. There were similar biomolecular signatures in other inflammatory states, such as sepsis. This enhances the potential for repurposing and generalizability in therapeutic approaches.

Parental Stress in a Pediatric Ophthalmology Population.

To determine the rate of parental stress within a pediatric ophthalmology population, parents in an urban or suburban community pediatric ophthalmology clinic were administered the Parental Stress Index Short Form survey. Demographic information and parental depression or anxiety data were collected and analyzed using an independent sample t-test and chi-squared analysis. Stress measures were recorded as percentiles. One hundred and twenty-one surveys revealed the following mean percentiles: Total Stress, 45.9 ± 22.4; Parental Distress (PD), 49.7 ± 19.8; and Parent Child Dysfunctional Interaction (P-CDI), 45.1 ± 23.6. The PD percentiles of the non-married parents, those with positive parental depression or anxiety scores, and those with a high school diploma or less were 55.9 ± 18.5 versus 45.2 ± 19.6, p < 0.01; 55.2 ± 18.6 versus 46.7 ± 19.9, p < 0.05; and 56.8 ± 18.2 versus 47.0 ± 19.8, p < 0.01, respectively. The parents with a high school diploma or less in a suburban environment demonstrated higher PD/P-CDI scores versus those of an urban population. Those with median household incomes (MHI) below USD 60,000 in both the total and suburban populations showed higher PD scores. There is no significant difference in parental stress between the pediatric ophthalmology patients and the general population. The parents who are unmarried, depressed, have a high school degree or less, or an MHI below USD 60,000 experience significantly higher stress levels.

Determining cost and placement decisions for moderate complexity NAATs for tuberculosis drug susceptibility testing.

BACKGROUND: Access to drug resistant testing for tuberculosis (TB) remains a challenge in high burden countries. Recently, the World Health Organization approved the use of several moderate complexity automated nucleic acid amplification tests (MC-NAAT) that have performance profiles suitable for placement in a range of TB laboratory tiers to improve drug susceptibility tests (DST) coverage. METHODS: We conducted cost analysis of two MC-NAATs with different testing throughput: Lower Throughput (LT, < 24 tests per run) and Higher Throughput (HT, upto 90+ tests per run) for placement in a hypothetical laboratory in a resource limited setting. We used per-test cost as the main indicator to assess 1) drivers of cost by resource types and 2) optimized levels of annual testing volumes for the respective MC-NAATs. RESULTS: The base-case per test cost of $18.52 (range: $13.79 - $40.70) for LT test and $15.37 (range: $9.61 - $37.40) for HT test. Per test cost estimates were most sensitive to the number of testing days per week, followed by equipment costs and TB-specific workloads. In general, HT NAATs were cheaper at all testing volume levels, but at lower testing volumes (less than 2,000 per year) LT tests can be cheaper if the durability of the testing system is markedly better and/or procured equipment costs are lower than that of HT NAAT. CONCLUSION: Assuming equivalent performance and infrastructural needs, placement strategies for MC-NAATs need to be prioritized by laboratory system's operational factors, testing demands, and costs.

Developmental Trajectories of Internalizing and Externalizing Symptoms in Youth and Associated Gender Differences: A Directed Network Perspective.

Psychopathology in youth is highly prevalent and associated with psychopathology in adulthood. However, the developmental trajectories of psychopathology symptoms, including potential gender differences, are markedly underspecified. The present study employed a directed network approach to investigate longitudinal relationships and gender differences among eight transdiagnostic symptom domains across three years, in a homogenous age sample of youth participants (n = 6,414; mean baseline age = 10.0 years; 78.6% White; Adolescent Brain Cognitive Development study). Anxious/depressed problems and aggressive behaviors were central symptoms and most predictive of increases in other symptom clusters at later timepoints. Rule-breaking behaviors, aggressive behaviors, and withdrawn/depressed problems emerged as bridge symptoms between externalizing and internalizing problems. Results supported cascade models in which externalizing problems predicted future internalizing problems, but internalizing problems also significantly predicted future externalizing problems, which is contrary to cascade models. Network structure, symptom centrality, and patterns of bridge symptoms differed between female and male participants, suggesting gender differences in the developmental trajectories of youth psychopathology. Results provide new insights into symptom trajectories and associated gender differences that may provide promising pathways for understanding disorder (dis)continuity and co-occurrence. The central and bridge symptoms identified here may have important implications for screening and early intervention for youth psychopathology.

Proteomic characterization of acute kidney injury in patients hospitalized with SARS-CoV2 infection.

BACKGROUND: Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. METHODS: Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N = 437), we identified 413 higher plasma abundances of protein targets and 30 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p < 0.05). Of these, 62 proteins were validated in an external cohort (p < 0.05, N = 261). RESULTS: We demonstrate that COVID-AKI is associated with increased markers of tubular injury (NGAL) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p < 0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2, trefoil factor 3, transmembrane emp24 domain-containing protein 10, and cystatin-C indicating tubular dysfunction and injury. CONCLUSIONS: Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

Acute kidney injury (AKI) is a sudden, sometimes fatal, episode of kidney failure or damage. It is a known complication of COVID-19, albeit through unclear mechanisms. COVID-19 is also associated with kidney dysfunction in the long term, or chronic kidney disease (CKD). There is a need to better understand which patients with COVID-19 are at risk of AKI or CKD. We measure levels of several thousand proteins in the blood of hospitalized COVID-19 patients. We discover and validate sets of proteins associated with severe AKI and CKD in these patients. The markers identified suggest that kidney injury in COVID-19 patients involves damage to kidney cells that reabsorb fluid from urine and reduced blood flow to the heart, causing damage to heart muscles. Our findings might help clinicians to predict kidney injury in patients with COVID-19, and to understand its mechanisms.

A study of gene expression in the living human brain.

A goal of medical research is to determine the molecular basis of human brain health and illness. One way to achieve this goal is through observational studies of gene expression in human brain tissue. Due to the unavailability of brain tissue from living people, most such studies are performed using tissue from postmortem brain donors. An assumption underlying this practice is that gene expression in the postmortem human brain is an accurate representation of gene expression in the living human brain. Here, this assumption - which, until now, had not been adequately tested - is tested by comparing human prefrontal cortex gene expression between 275 living samples and 243 postmortem samples. Expression levels differed significantly for nearly 80% of genes, and a systematic examination of alternative explanations for this observation determined that these differences are not a consequence of cell type composition, RNA quality, postmortem interval, age, medication, morbidity, symptom severity, tissue pathology, sample handling, batch effects, or computational methods utilized. Analyses integrating the data generated for this study with data from earlier landmark studies that used tissue from postmortem brain donors showed that postmortem brain gene expression signatures of neurological and mental illnesses, as well as of normal traits such as aging, may not be accurate representations of these gene expression signatures in the living brain. By using tissue from large cohorts living people, future observational studies of human brain biology have the potential to (1) determine the medical research questions that can be addressed using postmortem tissue as a proxy for living tissue and (2) expand the scope of medical research to include questions about the molecular basis of human brain health and illness that can only be addressed in living people (e.g., "What happens at the molecular level in the brain as a person experiences an emotion?").

Circulating proteins to predict COVID-19 severity.

Predicting COVID-19 severity is difficult, and the biological pathways involved are not fully understood. To approach this problem, we measured 4701 circulating human protein abundances in two independent cohorts totaling 986 individuals. We then trained prediction models including protein abundances and clinical risk factors to predict COVID-19 severity in 417 subjects and tested these models in a separate cohort of 569 individuals. For severe COVID-19, a baseline model including age and sex provided an area under the receiver operator curve (AUC) of 65% in the test cohort. Selecting 92 proteins from the 4701 unique protein abundances improved the AUC to 88% in the training cohort, which remained relatively stable in the testing cohort at 86%, suggesting good generalizability. Proteins selected from different COVID-19 severity were enriched for cytokine and cytokine receptors, but more than half of the enriched pathways were not immune-related. Taken together, these findings suggest that circulating proteins measured at early stages of disease progression are reasonably accurate predictors of COVID-19 severity. Further research is needed to understand how to incorporate protein measurement into clinical care.

Proteomic Characterization of Acute Kidney Injury in Patients Hospitalized with SARS-CoV2 Infection.

Background Acute kidney injury (AKI) is a known complication of COVID-19 and is associated with an increased risk of in-hospital mortality. Unbiased proteomics using biological specimens can lead to improved risk stratification and discover pathophysiological mechanisms. Methods Using measurements of ~4000 plasma proteins in two cohorts of patients hospitalized with COVID-19, we discovered and validated markers of COVID-associated AKI (stage 2 or 3) and long-term kidney dysfunction. In the discovery cohort (N= 437), we identified 413 higher plasma abundances of protein targets and 40 lower plasma abundances of protein targets associated with COVID-AKI (adjusted p <0.05). Of these, 62 proteins were validated in an external cohort (p <0.05, N =261). Results We demonstrate that COVID-AKI is associated with increased markers of tubular injury ( NGAL ) and myocardial injury. Using estimated glomerular filtration (eGFR) measurements taken after discharge, we also find that 25 of the 62 AKI-associated proteins are significantly associated with decreased post-discharge eGFR (adjusted p <0.05). Proteins most strongly associated with decreased post-discharge eGFR included desmocollin-2 , trefoil factor 3 , transmembrane emp24 domain-containing protein 10 , and cystatin-C indicating tubular dysfunction and injury. Conclusions Using clinical and proteomic data, our results suggest that while both acute and long-term COVID-associated kidney dysfunction are associated with markers of tubular dysfunction, AKI is driven by a largely multifactorial process involving hemodynamic instability and myocardial damage.

Human resource time commitments and associated costs of Community Caregiver outreach team operations in South Africa.

INTRODUCTION: In South Africa, Community Caregivers (CCGs) visit households to provide basic healthcare services including those for tuberculosis and HIV. However, CCG workloads, costs, and time burden are largely unknown. Our objective was to assess the workloads and operational costs for CCG teams operating in different settings in South Africa. METHODS: Between March and October 2018, we collected standardized self-reported activity time forms from 11 CCG pairs working at two public health clinics in Ekurhuleni district, South Africa. CCG workloads were assessed based on activity unit times, per-household visit time, and mean daily number of successful household visits. Using activity-based times and CCG operating cost data, we assessed CCG annual and per-household visit costs (USD 2019) from the health system perspective. RESULTS: CCGs in clinic 1 (peri-urban, 7 CCG pairs) and 2 (urban, informal settlement; 4 CCG pairs) served an area of 3.1 km2 and 0.6 km2 with 8,035 and 5,200 registered households, respectively. CCG pairs spent a median 236 minutes per day conducting field activities at clinic 1 versus 235 minutes at clinic 2. CCG pairs at clinic 1 spent 49.5% of this time at households (versus traveling), compared to 35.0% at clinic 2. On average, CCG pairs successfully visited 9.5 vs 6.7 households per day for clinics 1 and 2, respectively. At clinic 1, 2.7% of household visits were unsuccessful, versus 28.5% at clinic 2. Total annual operating costs were higher in clinic 1 ($71,780 vs $49,097) but cost per successful visit was lower ($3.58) than clinic 2 ($5.85). CONCLUSIONS: CCG home visits were more frequent, successful, and less costly in clinic 1, which served a larger and more formalized settlement. The variability in workload and cost observed across pairs and clinics suggests that circumstantial factors and CCG needs must be carefully assessed for optimized CCG outreach operations.

Beyond the abdominal and pelvic cavity: abdominal wall and spinal "Aunt Minnies".

Abdominal wall and spinal soft tissue findings are frequently encountered on CT or MR imaging of the abdomen and pelvis. Many of these entities have specific imaging findings, for which a definitive diagnosis can be made without the need for further work up. These abdominal wall and spinal findings may be diagnostically challenging for sub-specialized abdominal radiologists who are unfamiliar with their appearance and appropriate management. This review article describes and illustrates pathognomonic or characteristic abdominal wall and spinal pathologies, which reside outside the abdominopelvic cavity. The cases selected all have findings that allow a confident diagnosis without further imaging or intervention. The cases presented include myonecrosis, intramuscular abscess, myositis, iliopsoas bursitis, Morel-Lavallée lesion, hydrocele of canal of Nuck, Klippel Trenaunay Weber syndrome, neurofibroma with target sign, perineural cysts, filum terminale lipoma, calvarial bone flap, transverse rectus abdominis muscle (TRAM) flap, liposuction, and hidradenitis suppurativa, among others. Although not all-encompassing, this paper will help abdominal radiologists to accurately diagnose a variety of abdominal and pelvic extra-cavitary soft tissue pathologies by identifying key radiologic findings.