bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-eclampsia is a valuable opportunity to diagnose chronic kidney disease: a multicentre study
Authors: Cabiddu Gianfranca , Mannucci Claudia , Fois Antioco , Maxia Stefania , Chatrenet Antoine , Osadolor Sarah , Kimani Emily , Torreggiani Massimo , Attini Rossella , Masturzo Bianca , Cheve Marie Thérèse , Piccoli Giorgina Barbara
Published: July 2021

Background

Pre-eclampsia (PE) and chronic kidney disease (CKD) are known to be associated. Our objective was to assess the prevalence of CKD in a large multicentre cohort of women without acknowledged CKD who experienced a PE episode.

Methods

The setting for the study was France (Le Mans, Central France) and Italy (Cagliari, Sardinia). The study participants were patients who experienced PE in 2018–19, identified from the obstetric charts. Patients with known–acknowledged CKD were excluded. Only singletons were considered. Persistent (micro)albuminuria was defined as present and confirmed at least 3 months after delivery. CKD was defined according to the Kidney Disease Outcomes Quality Initiative guidelines; urinary alterations or low eGFR confirmed at a distance of at least 3 months, or morphologic changes. Patients were divided into four groups: evidence of CKD; no evidence of CKD; unclear diagnosis-ongoing work-up; or persistent microalbuminuria. The outcome ‘diagnosis of CKD’ was analysed by simple and multiple logistic regressions. Temporal series (week of delivery) were analysed with Kaplan–Meier curves and Cox analysis.

Results

Two hundred and eighty-two PE pregnancies were analysed (Le Mans: 162; Cagliari: 120). The incidence of CKD diagnosis was identical (Le Mans: 19.1%; Cagliari: 19.2%); no significant difference was found in unclear-ongoing diagnosis (6.2%; 5.8%) and microalbuminuria (10.5%; 5.8%). Glomerulonephritis and diabetic nephropathy were more frequent in Cagliari (higher age and diabetes prevalence), and interstitial diseases in Le Mans. In the multivariate logistic regression, CKD diagnosis was associated with preterm delivery (adjusted P = 0.035). Gestation was 1 week shorter in patients diagnosed with CKD (Kaplan–Meier P = 0.007). In Cox analysis, CKD remained associated with shorter gestation after adjustment for age and parity.

Conclusions

The prevalence of newly diagnosed CKD is high after PE (19% versus expected 3% in women of childbearing age), supporting a systematic nephrology work-up after PE.
Machine Learning-Based Prediction of Early Recurrence in Glioblastoma Patients: A Glance Towards Precision Medicine
Authors: Della Pepa Giuseppe Maria , Caccavella Valerio Maria , Menna Grazia , Ius Tamara , Auricchio Anna Maria , Sabatino Giovanni , La Rocca Giuseppe , Chiesa Silvia , Gaudino Simona , Marchese Enrico , Olivi Alessandro
Published: July 2021

BACKGROUND

Ability to thrive and time-to-recurrence following treatment are important parameters to assess in patients with glioblastoma multiforme (GBM), given its dismal prognosis. Though there is an ongoing debate whether it can be considered an appropriate surrogate endpoint for overall survival in clinical trials, progression-free survival (PFS) is routinely used for clinical decision-making.

OBJECTIVE

To investigate whether machine learning (ML)-based models can reliably stratify newly diagnosed GBM patients into prognostic subclasses on PFS basis, identifying those at higher risk for an early recurrence (≤6 mo).

METHODS

Data were extracted from a multicentric database, according to the following eligibility criteria: histopathologically verified GBM and follow-up >12 mo: 474 patients met our inclusion criteria and were included in the analysis. Relevant demographic, clinical, molecular, and radiological variables were selected by a feature selection algorithm (Boruta) and used to build a ML-based model.

RESULTS

Random forest prediction model, evaluated on an 80:20 split ratio, achieved an AUC of 0.81 (95% CI: 0.77; 0.83) demonstrating high discriminative ability. Optimizing the predictive value derived from the linear and nonlinear combinations of the selected input features, our model outperformed across all performance metrics multivariable logistic regression.

CONCLUSION

A robust ML-based prediction model that identifies patients at high risk for early recurrence was successfully trained and internally validated. Considerable effort remains to integrate these predictions in a patient-centered care context.
Spinal Arachnoid Webs: Presentation, Natural History, and Outcomes in 38 Patients
Authors: Laxpati Nealen , Malcolm James G , Tsemo Georges Bouobda , Mustroph Christian , Saindane Amit M , Ahmad Faiz , Refai Daniel , Gary Matthew F
Published: July 2021

BACKGROUND

Spinal arachnoid webs are rarely described bands of thickened arachnoid tissue in the dorsal thoracic spine. Much is unknown regarding their origins, risk factors, natural history, and outcomes.

OBJECTIVE

To present the single largest case series, detailing presenting symptoms and outcomes amongst operative and nonoperative patients, to better understand the role of intervention.

METHODS

This retrospective chart review identified 38 patients with arachnoid webs. Patient demographics, radiologic signs, symptoms, and surgical history data were extracted from the electronic medical record. Symptoms were divided by location and character. 28 patients were successfully contacted for follow up outcome surveys.

RESULTS

26 patients (68%) underwent surgical intervention, 12 (32%) were managed non-operatively. 15 (39%) patients had undergone a previous unsuccessful surgery at a different site for their symptoms prior to arachnoid web diagnosis. Commonly presenting symptoms included myelopathy (68%), focal thoracic back pain (68%), lower extremity weakness (45%), numbness and sensory changes (58%), and lower extremity radicular pain (42%), upper extremity weakness (24%), and radicular pain (37%). Focal thoracic pain was associated with thoracic level (P < .02). Myelopathic symptoms were less common in postoperative patients. Postoperative patients described significantly more upper extremity (P < .01) and thoracic (P < .01) numbness and paresthesias. Surveyed nonoperative patients universally described their symptoms as either stable or worsening.

CONCLUSION

Spinal arachnoid webs present with thoracic myelopathy and back pain but can also present with upper extremity symptoms. Surgical intervention stabilizes or improves symptoms and is well received. Nonoperative patients do not spontaneously improve.
Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Presence of Anti–SARS-CoV-2 Antibodies Among University Student Dormitory Residents, September–November 2020
Authors: Segaloff Hannah E , Cole Devlin , Rosenblum Hannah G , Lee Christine C , Morgan Clint N , Remington Patrick , Pitts Collin , Kelly Patrick , Baggott Jake , Bateman Allen , Somers Tarah , Ruff Jeanne , Payne David , Desamu-Thorpe Rodel , Foster Monique A , Currie Dustin W , Abedi Glen R , Westergaard Ryan , Hsu Christopher H , Tate Jaqueline E , Kirking Hannah L
Published: July 2021

Background

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks occurred at universities during Fall 2020, but little is known about risk factors for campus-associated infections or immunity provided by anti–SARS-CoV-2 antibodies in young adults.

Methods

We conducted surveys and serology tests among students living in dormitories in September and November to examine infection risk factors and antibody presence. Using campus weekly reverse-transcription polymerase chain reaction (RT-PCR) test results, the relationship between survey responses, SARS-CoV-2 antibodies, and infections was assessed.

Results

Of 6136 students, 1197 completed the survey and 572 also completed serologic testing in September compared with 517 and 414 in November, respectively. Participation in fraternity or sorority events (adjusted risk ratio [aRR], 1.9 [95% confidence interval {CI}, 1.4–2.5]) and frequent alcohol consumption (aRR, 1.6 [95% CI, 1.2–2.2]) were associated with SARS-CoV-2 infection. Mask wearing during social events (aRR, 0.6 [95% CI, .6–1.0]) was associated with decreased risk. None of the 20 students with antibodies in September tested positive for SARS-CoV-2 during the semester, while 27.8% of students who tested RT-PCR positive tested negative for antibodies in November.

Conclusions

Frequent drinking and attending social events were associated with SARS-CoV-2 infection. Antibody presence in September appeared to be protective from reinfection, but this finding was not statistically significant.
The “Three on a Stick” Incision—A Curvilinear Solution for the Occipital and Suboccipital Region
Authors: Kershenovich Amir
Published: July 2021

BACKGROUND

Different conditions of the posterior fossa such as Chiari malformations, tumors, and arachnoid cysts require surgery through a suboccipital approach, for which a typical midline vertical linear incision is used. Curvilinear incisions have been carried in all other scalp regions other than the sub region for better cosmetic outcomes; a vertical curvilinear incision in the occipital and suboccipital region has not been reported.

OBJECTIVE

To evaluate the cosmetic value and safety of the “3 on a stick” vertical suboccipital curvilinear incision.

METHODS

We compared curvilinear to linear incisions, considering the scar's width, color, how conspicuous, and how well the scar could be covered by hair naturally.

RESULTS

Between 2010 and 2016, 68 children with Chiari I malformation were surgically intervened. The curvilinear incision was performed in 56 (82.4%) while a linear incision in 12 (17.6%) children. There were only 2 (2.9%) wound related complications (superficial dehiscences) in the curvilinear group and 1 additional dehiscence in a linear incision case. There were no neural or vascular complications. Scars were very similar among the 2 groups; both were equally conspicuous but curvilinear ones seemed to get covered better by hair.

CONCLUSION

The “3 on a stick” curvilinear incision of the suboccipital region is safe and allows for better hair coverage of the scar. It can be used for multiple conditions requiring a midline suboccipital or even occipital approach, such as Chiari malformations, tumors, and cysts.
Technique to “Trap” a Segment of the Middle Meningeal Artery for Embolization of a Carotid Cavernous Fistula: 2-Dimensional Operative Video
Authors: Khorasanizadeh MirHojjat , Salih Mira , Harris Dominic , Ogilvy Christopher S
Published: July 2021

Transvenous embolization is the favored treatment for indirect carotid-cavernous fistulas (CCFs). However, transarterial embolization can be used as an alternative method when the venous route is inaccessible. We present the case of a 47-yr-old woman with a history of diplopia, headaches, and sixth cranial nerve (CN-VI) palsy who presented with acute worsening of headache and ophthalmoplegia and rise of intraocular pressures. Angiography demonstrated a left indirect CCF (dural arteriovenous malformation) with multiple arterial feeders from the internal carotid artery as well as the middle meningeal artery (MMA) (Barrow type D). Transvenous approach was attempted first but was unsuccessful due to difficult access to the cavernous sinus. Thus, transarterial embolization through the MMA feeding branches was planned. To avoid occluding distal branches of the MMA by Onyx, we coiled it distally. In addition, we used a scepter balloon proximally to prevent the reflux of Onyx into potential collaterals to cranial nerves from proximal MMA. After trapping a segment of the MMA, Onyx was injected into the CCF fistula through the small MMA feeders. A postembolization arteriogram showed obliteration of the CCF. The patient developed mild left facial nerve paresis on the first postoperative day (thought to be related to partial embolization of tiny arteries in the facial canal), which was resolving in the course of hospitalization. She remained neurologically stable, and was discharged on the third postoperative day. To the best of our knowledge, this is the first report of transarterial embolization of CCF by distal coiling and proximal ballooning to trap a segment of an artery. The authors hereby confirm that informed consent was obtained from the patient after thorough discussion of the procedure's rationale, risks, benefits, and alternatives.
Pole position: How plant cells polarize along the axes
Authors: Ramalho João Jacob , Jones Victor Arnold Shivas , Mutte Sumanth , Weijers Dolf
Published: July 2021

Having a sense of direction is a fundamental cellular trait that can determine cell shape, division orientation, or function, and ultimately the formation of a functional, multicellular body. Cells acquire and integrate directional information by establishing discrete subcellular domains along an axis with distinct molecular profiles, a process known as cell polarization. Insight into the principles and mechanisms underlying cell polarity has been propelled by decades of extensive research mostly in yeast and animal models. Our understanding of cell polarity establishment in plants, which lack most of the regulatory molecules identified in other eukaryotes, is more limited, but significant progress has been made in recent years. In this review, we explore how plant cells coordinately establish stable polarity axes aligned with the organ axes, highlighting similarities in the molecular logic used to polarize both plant and animal cells. We propose a classification system for plant cell polarity events and nomenclature guidelines. Finally, we provide a deep phylogenetic analysis of polar proteins and discuss the evolution of polarity machineries in plants.
Changes in Job Quality as People Work Beyond Pensionable Age in Sweden
Authors: Sacco Lawrence B , Cahill Kevin E , Westerlund Hugo , Platts Loretta G
Published: July 2021

Large numbers of people remain in paid work after pensionable age, often in bridge jobs or with reduced working hours. Remarkably, knowledge about the quality of these jobs relative to those taken prior to pension eligibility is very limited. In this paper, we examined changes in job quality among workers in their sixties in the context of contemporaneous changes in work intensity and employment characteristics. This study is based on data from the biennial Swedish Longitudinal Occupational Survey of Health (SLOSH, 2006–2018, n = 1890–3013). Job quality outcomes were physical (dangerous, strenuous or unpleasant work) and psychosocial (job strain, effort-reward imbalance, work time control) working conditions and job satisfaction. First difference estimation was used to observe within-individual wave-to-wave changes in job quality over ages 61/62–69/70. Changes in working hours, employment characteristics (shifting to a non-permanent contract, the private sector and self-employment) and health were included as covariates. The typical individual who worked beyond pensionable age experienced statistically significant improvements in job quality. Improvements in psychosocial working conditions and job satisfaction were larger for those who reduced working hours and shifted from permanent to non-permanent contracts, from the public into the private sector and from wage-and-salary to self-employment. Work beyond pensionable age is a distinctive period, characterized by employment that becomes more flexible and rewarding and less stressful. These improvements are a function of older individuals’ preferences and ability to work fewer hours and transition to new lines of work.
Geographic Distribution of Ophiosphaerella Species in the Mid-Atlantic United States
Authors: Hutchens Wendell J. , Henderson Caleb A. , Bush Elizabeth A. , Kerns James P. , McCall David S.
Published: July 2021

Spring dead spot (SDS) of bermudagrass (Cynodon dactylon) is primarily caused by Ophiosphaerella herpotricha and Ophiosphaerella korrae in North America. These two species respond differently to numerous management practices, grow optimally at different soil pH ranges, and differ in aggressiveness. Understanding the Ophiosphaerella species distribution in regions where SDS occurs will allow turfgrass managers to tailor their management practices toward the predominant species present. A survey was conducted in the Mid-Atlantic United States in which 1 to 14 samples of bermudagrass expressing SDS symptoms were taken from 51 athletic fields, golf courses, or sod farms across Delaware, Maryland, North Carolina, and Virginia. DNA was isolated from necrotic root and stolon tissue, amplified using species-specific primers, and detected in a real-time PCR assay. At least one isolate of O. herpotricha was recovered from 76% of the locations, and O. korrae was recovered from 73% of the locations. O. herpotricha was amplified from 55% of the samples, whereas O. korrae was amplified from 37% of the samples. There were distinct regions in the Mid-Atlantic in which either O. herpotricha or O. korrae was predominant. O. herpotricha was predominant in western Virginia, central North Carolina, Delaware, and eastern Maryland. However, O. korrae was predominant in central Maryland and Virginia as well as eastern Virginia and North Carolina. O. herpotricha was isolated from certain cultivars more frequently than O. korrae and vice versa. These survey results elucidate the geographic distribution of O. herpotricha and O. korrae throughout the Mid-Atlantic United States.
Application of Human Factors Methods to Ensure Appropriate Infant Identification and Abduction Prevention Within the Hospital Setting
Authors: Webster Kristen L. W. , Stikes Reetta , Bunnell Lisa , Gardner Amanda , Petruska Sara
Published: July 2021

Infant misidentification and abduction are recognized as “never” events for hospitals in the United States. As near misses are often unreported, root cause analysis of observed near misses may fail to uncover important contributors. We utilized failure mode and effects analysis to proactively identify and eliminate or reduce the risk of infant misidentification or abduction. We prioritized action plans based upon the highest risk priority failures and developed steps to eliminate the gaps in the infant identification process and the security within the Center for Women & Infants. The analysis identified 28 failure modes. Team discussion of the failure modes also yielded several collateral benefits of improvements in the unit climate. We present and discuss the action plans that were undertaken by the hospital to increase patient safety and reduce the risk of infant misidentification and abduction.
Comparing JM-105 and MBJ-20 Transcutaneous Bilirubinometers According to the Area Tested in Ethnically Diverse Late-Preterm and Term Neonates
Authors: Khajehei Marjan , Chua Seng Chai , Gidaszewski Beata , Swain Julie
Published: July 2021

This study aims to evaluate the correlation between the results of transcutaneous bilirubin (TcB) levels measured by the 2 transcutaneous bilirubinometers according to the area tested and to compare the TcB measurements and the serum bilirubin (SBR) levels. We screened 78 neonates born at more than 35 weeks of gestation and aged less than 168 hours for jaundice. We used JM-105 and MBJ-20 to measure the TcB at the forehead and the chest. For newborns who had high TcB measurements, we obtained blood samples during the subsequent 30 minutes. There was a strong correlation between the TcB measurements by JM-105 and MBJ-20 and this correlation was stronger when they were used on the sternum. The mean differences between the TcB measurements on the forehead and the sternum and the SBR levels were similar for the JM-105 and the MBJ-20. There was a strong correlation between SBR and the measurements using the 2 devices on the sternum (JM-105: r = 0.805; MBJ-20: r = 0.801), unlike measurements taken on the forehead by each device (r = 0.777 and r = 0.751, respectively). Both devices had high sensitivity and negative predictive values at SBR level of less than 230 μmol/L (<13.4 mg/dL) and high specificity and positive predictive values at SBR level of 230 μmol/L and greater (>13.4mg/dL). Both devices equally overestimated the actual SBR and had more reliable results if used on the sternum.
The American College of Nurse-Midwives' Benchmarking Project
Authors: Emeis Cathy L. , Jolles Diana R. , Perdion Karen , Collins-Fulea Catherine
Published: July 2021

Maternal and newborn outcomes in the United States are suboptimal. Care provided by certified nurse-midwives and certified midwives is associated with improved health outcomes for mothers and newborns. Benchmarking is a process of continuous quality assurance providing opportunities for internal and external improvement. Continuous quality improvement is a professional standard and expectation for the profession of midwifery. The American College of Nurse-Midwives Benchmarking Project is an example of a long-standing, midwifery-led quality improvement program. The project demonstrates a program for midwifery practices to display and compare their midwifery processes and outcomes of care. Quality metrics in the project reflect national quality measures in maternal child health while intentionally showcasing the contributions of midwives. The origins of the project and the outcomes for data submitted for 2019 are described and compared with national rates. The American College of Nurse-Midwives Benchmarking Project provides participating midwifery practices with information for continuous improvement and documents the high quality of care provided by a sample of midwifery practices.
Hens to Humans
Authors: Berdanier Carolyn D.
Published: July 2021

Beriberi was first described by Chinese physicians around 300 ad long before thiamine was discovered and long before medicine had advanced to the understanding of how nutrients in food were important to disease prevention. The connection between the loss in nutrient value due to the processing of specific foods had yet to be realized. As with many of our discoveries in nutrition, it took man centuries to identify the nutrient that when deficient caused beriberi. Once the initial link was made, then discoveries of how thiamine functions and how much humans need came together in rapid order.
The Association Between the Nordic-Style Diet Score and Metabolic Syndrome and Obesity in Tehranian Adults
Authors: Noruzi Zahra , Jayedi Ahmad , Farazi Mena , Moosavi Hanieh , Janbozorgi Nasim , Djafarian Kurosh , Shab-Bidar Sakineh
Published: July 2021

Objective

We aimed to assess the association of the Nordic-style diet score with general and abdominal obesity and metabolic syndrome (MetS) in a population-based cross-sectional study of Iranian adults.

Methods

We recruited 843 participants with an age range of 18 to 65 years (mean [SD] age, 44.8 [10.7] years). Dietary intake was assessed by a 168-item semiquantitative food frequency questionnaire. The Nordic-style diet score was calculated by using the median intake of 6 food groups including rye and whole grains, oatmeal, cabbage and vegetables, apples and pears, root vegetables, and fish. The odds ratio (OR) and 95% CI of obesity and MetS across tertiles of the Nordic diet score were calculated by logistic regression analysis with adjustment for age, sex, energy intake, physical activity, smoking status, education, and marital status.

Results

A higher score of adherence to the Nordic-style diet score was not associated with general and central adiposity and MetS. With regard to components of the MetS, those in the second tertile of the Nordic-style diet score were at a lower risk of increased serum cholesterol concentration (OR, 0.61; 95% CI, 0.43–0.86; P = .006), and high systolic (OR, 0.65; 95% CI, 0.42–1.00; P = .05) and diastolic (OR, 0.70; 95% CI, 0.46–1.06; P = .09) blood pressure. There was no association between the Nordic-style diet score and other components of the MetS.

Conclusion

This study showed that there was no significant relationship between Nordic-style diet score and abdominal and general obesity and MetS. Adopting a Nordic-style diet may be associated with lower serum cholesterol concentration and blood pressure.
Multi-omics insights into the biological mechanisms underlying gene-by-lifestyle interactions with smoking and alcohol consumption detected by genome-wide trans-ancestry meta-analysis
Authors: Majarian Timothy D. , Bentley Amy R. , Laville Vincent , Brown Michael R. , Chasman Daniel I. , Cupples L. Adrienne , de Vries Paul S. , Feitosa Mary F. , Franceschini Nora , Gauderman W. James , Levy Daniel , Morrison Alanna C. , Province Michael , Rao Dabeeru C. , Schwander Karen , Sung Yun Ju , Rotimi Charles N. , Aschard Hugues , Gu C. Charles , Manning Alisa K.
Published: July 2021

Gene-lifestyle interaction analyses have identified genetic variants whose effect on cardiovascular risk-raising traits is modified by alcohol consumption and smoking behavior. The biological mechanisms of these interactions remain largely unknown, but may involve epigenetic modification linked to perturbation of gene expression. Diverse, individual-level datasets including genotypes, methylation and gene expression conditional on lifestyle factors, are ideally suited to study this hypothesis, yet are often unavailable for large numbers of individuals. Summary-level data, such as effect sizes of genetic variants on a phenotype, present an opportunity for multi-omic study of the biological mechanisms underlying gene-lifestyle interactions. We propose a method that unifies disparate, publicly available summary datasets to build mechanistic hypotheses in models of smoking behavior and alcohol consumption with blood lipid levels and blood pressure measures. Of 897 observed genetic interactions, discovered through genome-wide analysis in diverse multi-ethnic cohorts, 48 were identified with lifestyle-related differentially methylated sites within close proximity and linked to target genes. Smoking behavior and blood lipids account for 37 and 28 of these signals respectively. Five genes also showed differential expression conditional on lifestyle factors within these loci with mechanisms supported in the literature. Our analysis demonstrates the utility of summary data in characterizing observed gene-lifestyle interactions and prioritizes genetic loci for experimental follow up related to blood lipids, blood pressure, and cigarette smoking. We show concordance between multiple trait-or exposure-related associations from diverse assays, driving hypothesis generation for better understanding gene-lifestyle interactions.
A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia
Authors: Whittaker Danielle E. , Oleari Roberto , Gregory Louise C. , Le Quesne-Stabej Polona , Williams Hywel J. ,   GOSgene, Torpiano John G. , Formosa Nancy , Cachia Mario J. , Field Daniel , Lettieri Antonella , Ocaka Louise , Paganoni Alyssa J.J. , Rajabali Sakina , Riegman Kimberley L. , De Martini Lisa Benedetta , Chaya Taro , Robinson Iain C.A.F. , Furukawa Takahisa , Cariboni Anna , Basson M. Albert , Dattani Mehul T.
Published: July 2021

PRDM13 (PR Domain containing 13) is a putative chromatin modifier and transcriptional regulator that functions downstream of the transcription factor PTF1A, which in turn controls GABAergic fate in the spinal cord and neuronal development in the hypothalamus. Here, we report a novel, recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. We investigated the development of hypothalamic neurons and the cerebellum in mice homozygous for a Prdm13 mutant allele.

A significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone were observed. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Phenotypically, mice lacking PRDM13 displayed cerebellar hypoplasia, normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of kisspeptin neuron development in the hypothalamus, providing a mechanistic explanation for the co-occurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.
Transcriptomic signature on Hantavirus Cardiopulmonary Syndrome patients, reveals an increased interferon response as a hallmark of critically ill patients
Authors: Ribeiro Grazielle E. , Duran-Jara Eduardo , Perez Ruth , Cuiza Analia , Leon Luis E. , Martínez-Valdebenito Constanza , Le Corre Nicole , Ferres Marcela , Ferreira Leonila , Rioseco Maria Luisa , Gavilán Jorge , Arancibia Francisco , Graf Jerónimo , Lopez Rene , Perez Jose Luis , Calvo Mario , Mertz Gregory J , A.Vial Pablo , Vial Cecilia ,   the hantavirus study group
Published: July 2021

New World hantaviruses are important human pathogens that can cause a severe zoonotic disease called hantavirus cardiopulmonary syndrome (HCPS). HCPS patients can progress quickly to a severe condition with respiratory failure and cardiogenic shock that can be fatal in 30% of the cases. The role of the host’s immune responses in this progression towards HCPS remains elusive. In this study, 12 patients hospitalized with severe HCPS were analyzed using a transcriptome approach combined with clinical laboratory data to gain a better insight into factors associated with a severe clinical course. Patients were further classified in two levels of severity, a first group that required mechanical ventilation and vasoactive drugs (VM+VD) and a second group that also needed ECMO or died (ECMO/Fatal). Their transcriptional profile was compared during acute (early and late) and convalescent phases. Our results showed that overexpression of the interferon response is correlated with a worse (ECMO/Fatal) outcome and an increased viral load and proinflammatory cytokines in the early-acute-phase. This report provides insights into the differences in innate immune activation between severe patients that associates with different clinical outcomes, using a non-biased approximation.

Author Summary

Hantavirus are rodent-borne zoonotic pathogens that when transmitted to humans cause two diseases: hantavirus renal syndrome in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. The latter, the goal of this work, is a highly lethal disease with a case fatality rate of 30%. Moreover no specific treatment or vaccine is available for this disease. In this study, we analyzed hospitalized HCPS patients with severe disease, to understand how they respond to hantavirus infection. We used a method that can measure every mRNA that is being transcribed in one moment (transcriptome analysis) and thus provide an accurate idea of how cells (specifically peripheral blood mononuclear cells) are responding to infection. The knowledge gained in this study helps us further understand the pathogenesis of this disease and might help us to design specific therapies to treat it.
In situ transcriptional profile of a germinal center plasmablastic burst hints at MYD88/CD79B mutants-enriched Diffuse Large B-cell Lymphomas
Authors: L’Imperio Vincenzo , Morello Gaia , Vegliante Maria Carmela , Cancila Valeria , Bertolazzi Giorgio , Mazzara Saveria , Belmonte Beatrice , Balzarini Piera , Corral Lilia , Napoli Arianna Di , Facchetti Fabio , Pagni Fabio , Tripodo Claudio
Published: July 2021

The germinal center (GC) reaction results in the selection of B-cells acquiring effector Ig secreting ability by progressing towards plasmablastic differentiation. This transition is associated with exclusion from the GC microenvironment. The aberrant expansion of plasmablastic elements within the GC fringes configures an atypical condition, the biological characteristics of which have not been defined yet. We investigated the in situ immunophenotypical and transcriptional characteristics of a non-clonal germinotropic expansion of plasmablastic elements (GEx) occurring in the tonsil of a young patient. Compared to neighboring GC and peri-follicular regions, the GEx showed a distinctive signature featuring key regulators of plasmacytic differentiation, cytokine signaling, and cell metabolism. The GEx signature was tested in the setting of diffuse large B-cell lymphoma (DLBCL) as a prototypical model of lymphomagenesis encompassing transformation at different stages of GC and post-GC functional differentiation. The signature outlined DLBCL clusters with different immune microenvironment composition and enrichment in genetic subtypes.

Significance

This report represents the first insight into the transcriptional features of a germinotropic plasmablastic burst, shedding light into the molecular hallmarks of B cells undergoing plasmablastic differentiation and aberrant expansion within the non-canonical setting of the GC microenvironment.
Estimates of Single Dose and Full Dose BNT162b2 Vaccine Effectiveness among USAF Academy cadets, 1 Mar - 1 May 2021
Authors: Wickert Douglas P. , Almand Erin A. , Baldovich Kevin J. , Cullenbine Christopher A. , Huckstep Odaro J. , Rohrer Joseph W. , Sitko John C. , Steel J. Jordan , Hasstedt Steven C.M.
Published: July 2021

Beginning in early March 2021 and continuing through May 2021, the USAF Academy began vaccinating cadets for protection against the SARS-CoV-2 virus with the BNT162b2 (Pfizer-BioNTech) mRNA vaccine. During this period, vaccination of the almost 4200 cadet population increased from 3% to 85% and prevalence of COVID-19 in the cadet population was constant at approximately 0.4% as indicated by weekly surveillance testing. In this study, vaccine effectiveness at preventing infection is estimated by comparing infection risk as a function of time since vaccination. A statistically significant four-fold reduction in infection risk was observed 14 days after the first vaccine dose and an eleven-fold reduction in infection risk was observed in fully vaccinated cadets. Overall, the Pfizer-BioNTech vaccine was 91% (95% confidence interval = 55-99%) effective at preventing infection in healthy young adults (17-26 years of age) in a university setting and military training environment.
Machine Learning Methods to Predict Survival in Patients Following Traumatic Aortic Injury
Authors: Shiban Nisreen , Gaul Joshua , Zhan Henry , Elhabr Andrew , Kokabi Nima , Johnson Jamlik-Omari , Hanna Tarek , Schrager Justin , Gichoya Judy , Banerjee Imon , Trivedi Hari
Published: July 2021

The National Trauma Data Bank (NTDB) is a resource of diagnostic, treatment, and outcomes information in trauma patients. We leverage the NTDB and machine learning techniques to predict survival following traumatic aortic injury. We create two predictive models using the NTDB – 1) using all data and, 2) using only data available in the first hour after arrival (prospective data). Seven discriminative model types were tested before and after feature engineering to reduce dimensionality. The top performing model was XGBoost, achieving an overall accuracy of 0.893 using all data and 0.855 using prospective data. Feature engineering improved performance of all models. Glasgow Coma Scale score was the most important factor for survival, and thoracic endovascular aortic repair was more common in patients that survived. Smoking, pneumonia, and urinary tract infection predicted poor survival. We also note concerning disparities in outcomes for black and uninsured patients that may reflect differences in care.
Assessing optimal time between doses in two-dose vaccination regimen in an ongoing epidemic of SARS-CoV-2
Authors: Ferreira Leonardo Souto , Canton Otavio , Paixão da Silva Rafael Lopes , Poloni Silas , Sudbrack Vítor , Borges Marcelo Eduardo , Franco Caroline , Darcie Marquitti Flávia Maria , de Moraes José Cássio , de Sousa Mascena Veras Maria Amélia , André Kraenkel Roberto , Coutinho Renato Mendes
Published: July 2021

The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals.

Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. Simulations for each time window and for different types of vaccines and production rates were run to find the optimal time window between doses, that is, the one that minimizes the number of deaths.

We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to apply the second dose as soon as possible, while for high first-dose efficacy, the optimal window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the optimal window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.
Effects of Various Policy Options on COVID-19 Cases in Nova Scotia including Vaccination Rollout Schedule: A Modelling Study
Authors: Gillis Melissa , Saif Ahmed , Murphy Matthew , Kamal Noreen
Published: July 2021

Background

The COVID-19 pandemic presents a significant challenge to minimize mortality and hospitalizations due to this disease. Vaccinations have begun to roll-out; however, restriction policies required during and after the rollout remain uncertain. A susceptible-exposed-infected-recovered (SEIR) model was developed for Nova Scotia, and it accounted for the province’s policy interventions, demographics, and vaccine rollout schedule.

Methods

A modified SEIR model was developed to simulate the spread and outcomes from COVID-19 in Nova Scotia under different policy options. The model incorporated the age distribution and co-morbidity of the province. A system dynamics model was developed in Vensim. Several scenarios were run to determine the effects of various policy options and loosening of restrictions during and after the vaccine roll-out period.

Results

When restrictions policy include moderate closure of businesses, restricting travel to Atlantic Canada, and the mandating of masks and physical distancing, the number of cumulative infections after 110 days was less than 120. However, if national travel was opened by July 5 2021 and there were no restrictions by September 2021, the number of active infections will peak at 6,114 by February 16 2022, and there will be a peak of 104 hospitalizations on February 16 2022. Immediate opening of travel and all restrictions on March 15, 2021 will result in 71,731 active infections by June 4 2021.

Discussion

Moderate restrictions will be required even after the population is fully vaccinated in order to avoid a large number of infections and hospitalizations because herd immunity is not reached due to children under 12 not being vaccinated, the efficacy of the vaccine, and the portion of the population that will choose not to be vaccinated.
Effects of SARS-CoV-2 P.1 introduction and the impact of COVID-19 vaccination on the epidemiological landscape of São José Do Rio Preto, Brazil
Authors: Banho Cecília Artico , Sacchetto Lívia , Campos Guilherme Rodrigues Fernandes , Bittar Cíntia , Possebon Fábio Sossai , Ullmann Leila Sabrina , Marques Beatriz de Carvalho , da Silva Gislaine Ceslestino Dutra , Moraes Marília Mazzi , Parra Maisa Carla Pereira , Negri Andreia Francesli , Boldrin Ana Carolina , Barcelos Michela Dias , dos Santos Thayza M. I. L. , Milhim Bruno H. G. A. , da Rocha Leonardo Cecílio , Dourado Fernanda Simões , dos Santos Andresa Lopes , Ciconi Victoria Bernardi , Patuto Caio , Versiani Alice Freitas , da Silva Rafael Alves , Lobl Edoardo Estevam de Oliveira , Hernandes Victor Miranda , Zini Nathalia , Pacca Carolina Colombelli , Estofolete Cássia Fernanda , Ferreira Helena Lage , Rahal Paula , Araújo João Pessoa , Cohen Jamie A. , Kerr Cliff C. , Althouse Benjamin M. , Vasilakis Nikos , Nogueira Mauricio Lacerda
Published: July 2021

The emergence of the new Brazilian variant of concern, P.1 lineage (Gamma), raised concern about its impact on the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Using 272 whole-genome sequences combined with epidemiological data, we showed that P.1 introduction in São José do Rio Preto, São Paulo, Brazil, was followed by the displacement of eight circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection. Our findings support that the P.1 variant is associated with an increase in mortality risk and severity of COVID-19 cases in younger aged groups, which corresponds to the unvaccinated population at the time. Moreover, our data highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.
An Oral SARS-CoV-2 Mpro Inhibitor Clinical Candidate for the Treatment of COVID-19
Authors: Owen Dafydd R , Allerton Charlotte M N , Anderson Annaliesa S , Aschenbrenner Lisa , Avery Melissa , Berritt Simon , Boras Britton , Cardin Rhonda D , Carlo Anthony , Coffman Karen , Dantonio Alyssa , Di Li , Eng Heather , Ferre RoseAnn , Gajiwala Ketan S , Gibson Scott A , Greasley Samantha E , Hurst Brett L , Kadar Eugene P , Kalgutkar Amit S , Lee Jack C , Lee Jisun , Liu Wei , Mason Stephen W , Noell Stephen , Novak Jonathan J , Obach R Scott , Ogilvie Kevin , Patel Nandini C , Pettersson Martin , Rai Devendra K , Reese Matthew R , Sammons Matthew F , Sathish Jean G , Singh Ravi Shankar P , Steppan Claire M , Stewart Al E , Tuttle Jamison B , Updyke Lawrence , Verhoest Patrick R , Wei Liuqing , Yang Qingyi , Zhu Yuao
Published: July 2021

The worldwide outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an established global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to counter the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity, and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency, in a phase I clinical trial in healthy human participants.
Clinical Trial Registration ID #: NCT04756531
Estimation of the onset ratio and the number of asymptomatic patients of COVID-19 from the proportion of untraceable patients
Authors: Odagaki Takashi
Published: July 2021

A simple method is devised to estimate the onset ratio of COVID-19 patients from the proportion of untraceable patients tested positive, which allows us to obtain the number of asymptomatic patients, the number of infectious patients and the effective reproduction number. The recent data in Tokyo indicate that there are about six to ten times as many infectious patients in the city as the daily confirmed new cases. It is shown that, besides social distancing and use of effective masks, a quarantine measure on non-symptomatic patients is critically important in controlling the pandemic.
Robust image-based risk predictions from the deep learning of lung tumors in motion
Authors: Bajaj Amishi , Teo P. Troy , Randall James , Lou Bin , Shah Jainil , Gopalakrishnan Mahesh , Kamen Ali , Abazeed Mohamed E.
Published: July 2021

Introduction

Deep learning (DL) models that use medical images to predict clinical outcomes are poised for clinical translation. For tumors that reside in organs that move, however, the impact of motion (i.e. degenerated object appearance or blur) on DL model accuracy remains unclear. We examine the impact of tumor motion on an image-based DL framework that predicts local failure risk after lung stereotactic body radiotherapy (SBRT).

Methods

An IRB-approved study (NU00212113) was used to identify patients treated with lung SBRT. Pre-therapy free breathing (FB) CT images from 849 patients were input into a multi-task deep neural network to generate an image fingerprint (or DL score) that predicts time-to-event local failure outcomes. The impact of tumor motion was examined on the DL scores for a hold-out set comprising 228 image series from 19 patients comprising: (1) FB CT, (2) four-dimensional (4D) CT, and (3) maximum-intensity projection (MIP) images.

Findings

Variance in image-derived DL scores were associated with tumor motion (R2 = 0.45). Specifically, DL score variance was deterministic with undulations in phase with the respiratory cycle (R2 = 0.77-0.99). DL scores, but not tumor volumes, peaked near end-exhalation (∼50% phase). The mean of the scores derived from 4D CT images and the score obtained from FB CT images were highly associated (Pearson r = 0.99). MIP-derived DL scores were significantly higher than 4D- or FB-derived risk scores (p < 0.0001).

Interpretation

We show that an image-based DL risk score derived from a series of four-dimensional CT images varies in a deterministic, sinusoidal trajectory in phase with the respiratory cycle. These results indicate that deep learning models of tumors in motion can be robust to fluctuations in object appearance due to movement and can guide standardization processes in the clinical translation of DL models for patients with lung cancer.