bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of MRI in Children With Congenital Limb Deficiencies With Associated Scoliosis
Authors: Gettys Franklin K. , Carpenter Ashley , Stasikelis Peter J.
Published: December 2019

Background:

The association of scoliosis and congenital limb deficiency has been well described. However, the incidence of neural axis abnormalities in this population is not known. The ability to assess the neural axis by physical examination may be limited in patients with a limb deficiency. Although mobility of the spine is important for all children, it can be especially so in children with a limb deficiency. As spinal fusion in children with limb deficiency potentially has more functional impact, detecting reversible forms of scoliosis seems particularly important.

Methods:

Retrospective review of children treated at 1 institution between 1990 and 2017 with both a diagnosis of a congenital limb deficiency, upper or lower, and scoliosis. Children were excluded if they had any neurological difference on history or physical examination, if they had sacral agenesis or spina bifida, or if their limb deficiency was related to trauma or early amniotic rupture sequence.

Results:

Twenty-four children were identified, 11 with lower extremity deficiency, 14 with upper extremity deficiency with 1 having both. Fifteen children demonstrated neural axis abnormalities, 6 (40%) required neurosurgery. Five (45%) of 11 lower extremity deficiency children had MRI findings, 3 of these needing neurosurgery. Of the 14 upper extremity deficiency children, 10 had MRI changes, and 3 required neurosurgery. Eight children with congenital scoliosis, 5 had MRI findings, with 4 children requiring neurosurgery. The other 16 children had scoliosis without vertebral abnormalities, 10 had MRI findings, and 2 required neurosurgery.

Conclusions:

There is a high incidence of neural axis abnormalities (63%) in children with congenital limb deficiencies and scoliosis. A large portion of these require neurosurgical intervention. MRI should be considered soon after presentation in this population of children.

Level of Evidence:

Level IV.

Design:

Retrospective cohort.
Mortality Prediction in Rural Kenya: A Cohort Study of Mechanical Ventilation in Critically Ill Patients
Authors: Parker Robert K. , Mwachiro Elizabeth B. , Mwachiro Michael M. , Pletcher Jocelyn , Parker Andrea S. , Many Heath R.
Published: December 2019

Importance:

Critical care is expanding in low- and middle-income countries. Yet, due to factors such as missing data and different disease patterns, predictive scores often fail to adequately predict the high rates of mortality observed.

Objectives:

We evaluated multiple prognostic models for the outcome of mortality in critically ill, mechanically ventilated patients in rural Kenya and examined factors contributing to mortality in our setting.

Design, Setting, and Participants:

A prospective cohort study was conducted on mechanically ventilated patients in rural Kenya. Consecutive patients 16 years old and older initiated on mechanical ventilation between January 1, 2016, and April 30, 2017, at Tenwek Hospital were included. Demographic data, clinical characteristics, and patient outcomes were collected during routine clinical care.

Main Outcomes and Measures:

We assessed the discrimination and calibration of multiple previously-described models for mortality: Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, quick Sequential Organ Failure Assessment, Simplified Acute Physiology Score II, Modified Early Warning Score, Tropical Intensive Care Score, Rwanda-Mortality Predictive Model, Vitals score (validated in Tanzania), and Vitals score for sepsis (validated in Uganda). Factors most associated with mortality were analyzed in our cohort utilizing stepwise regression.

Results:

Among the final cohort of 300 patients, the overall mortality rate was 60.7%, the average age was 39.9 years, 65% were male, and 33% were seen at an outside facility prior to admission to the critical care unit. Missing variables occurred in patients for numerous models but were complete in most adapted to resource-limited settings. Models displayed moderate prediction of mortality and variable discrimination area under the receiver operating characteristic curves (and Hosmer-Lemeshow chi-square statistic) of 0.77 (22.4) for Acute Physiology and Chronic Health Evaluation II, 0.70 (3.4) for Modified Early Warning Score, 0.65 (0.16) for quick Sequential Organ Failure Assessment, 0.55 (18.4) for Simplified Acute Physiology Score II and 0.74 (9.2) for Rwanda-Mortality Predictive Model, 0.72 (0.12) for Vitals Tanzania, 0.68 (14.7) for Vitals Uganda, and 0.65 (13.9) for Tropical Intensive Care Score. Variables associated with increased mortality in our population were hypotension, infection, traumatic brain injury, and hematocrit.

Conclusions and Relevance:

Overall, survival for critically ill patients in rural Kenya was poor, but predictable with contributing factors. Models designed for resource-constrained settings had favorable discrimination and better calibration for mortality prediction than high-resource models in our population of mechanically ventilated, critically ill patients in rural Kenya.
Community Experience With Acute Respiratory Distress Syndrome in the Prone Position
Authors: Khan Fahmida , Fistler Christa R. , Mixell Jefferson , Caplan Richard , Vest Michael T.
Published: December 2019

Objectives:

Mechanical ventilation in the prone position has been shown to improve outcomes in randomized trials of patients with moderate to severe acute respiratory distress syndrome and is recommended in clinical practice guidelines. However, data is lacking on the results of attempts to implement this practice in the community outside of clinical trials. To describe our early outcomes implementing mechanical ventilation in the prone position.

Design:

Retrospective cohort study.

Setting:

Medical intensive care unit of a large community-based teaching hospital.

Participants:

All patients ventilated in the prone position between June 2013 and October 2016.

Measurements and Main Results:

We describe patient characteristics, mortality, and frequency of complications (such as skin breakdown and accidental extubation) at our center. Eighty-one patients with a mean age of 55 years underwent mechanical ventilation in the prone position during the study period. Most patients also received vasopressors, neuromuscular blockade, and steroids. Overall mortality was 43%. The duration of the first proning session ranged from 1.5 to 40.5 hours. Mortality was lower (34%) in those ventilated in the prone position for more than 16 hours during the first session. In the 50 patients without treatment limitations, only 14% expired. There were no accidental extubations during prone positioning. Most of those who died had limitations placed on treatment prior to death.

Conclusions:

Overall mortality was higher in our cohort than in the randomized trial. However, differences such as lack of stabilization period, different cultures impacting end-of-life decisions, and timing of enrollment in the course of illness limit interpretation of this comparison. This exercise allows identification of areas for future quality improvement efforts such as increasing the duration of some proning sessions. Complications of prone positioning were uncommon.
National organization of uterine cervical cancer screening and social inequality in France
Authors: Raginel Thibaut , de Mil Rémy , Garnier Anne , Launoy Guy , Guittet Lydia
Published: December 2019

Some of the inequality in uterine cervical cancer (UCC) screening uptake are due to the socioeconomic deprivation of women. A national organized screening programme has proven to be effective in increasing the uptake, but may increase socioeconomic inequality. Therefore, we compared inequality in uptake of UCC screening between two French departments, one of which is experimenting an organized screening programme. We used reimbursement data from the main French health insurance scheme to compare screening rates in the municipalities of the two departments over a three-year period. The experimental department had higher screening rates, but the increase in deprivation in municipalities had a greater effect on the decrease in participation in this department. Moreover, while screening rates were higher in urban areas, the negative effect of deprivation on participation was greater in rural areas. Although these departments were compared at the same time under different conditions, socioeconomic inequality between them may have been greater before the experimentation started. However, screening may have led to an increase in socioeconomic inequality between women screened. Special attention must be paid to changes in socioeconomic and geographic inequality in the uptake of UCC screening when the programme is rolled out nationally.
Clinico-neuropathological features of isocitrate dehydrogenase 2 gene mutations in lower-grade gliomas
Authors: Wang Lei-Ming , Li Zhuo , Piao Yue-Shan , Cai Yan-Ning , Zhang Li-Yan , Ge Hai-Jing , Xu Wei-Wei , Lu De-Hong
Published: December 2019

Background:

Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lower-grade gliomas that carry IDH2 mutations.

Methods:

Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.

Results:

Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively).

Conclusions:

IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.
Latest clinical evidence of maintenance therapy in ovarian cancer
Authors: Walsh Christine S.
Published: December 2019

Purpose of review

To summarize the data supporting the use of maintenance therapy in ovarian cancer treatment.

Recent findings

Since December 2016, the United States Food and Drug Administration has approved four drugs for six different ovarian cancer maintenance indications based on the results of clinical trials demonstrating efficacy and tolerability. These include antiangiogenesis and poly (adenosine diphosphate-ribose) inhibitors (PARP inhibitors). Four drugs are approved for use in maintenance therapy for recurrent ovarian cancer, including bevacizumab (GOG-0213 and OCEANS), niraparib (NOVA), olaparib (Study 19 and SOLO2) and rucaparib (ARIEL3). Two drugs are approved for use in maintenance therapy in newly diagnosed ovarian cancer, including bevacizumab (GOG-0218) and olaparib (SOLO1). New data were reported at the European Society for Medical Oncology Congress in October 2019 that may lead to the approval of additional strategies in front-line maintenance, including the use of niraparib (PRIMA), veliparib (VELIA) and bevacizumab + olaparib (PAOLA).

The landscape of maintenance treatment options for ovarian cancer has been rapidly expanding and continues to evolve as new data emerge. Currently approved strategies include antiangiogenesis and PARP inhibitor treatments.
IMPAIRED DARK ADAPTATION ASSOCIATED WITH A DISEASED BRUCH MEMBRANE IN PSEUDOXANTHOMA ELASTICUM
Authors: Hess Kristina , Gliem Martin , Birtel Johannes , Müller Philipp , Hendig Doris , Andrews Colm , Murray Ian J. , Holz Frank G. , Charbel Issa Peter
Published: December 2019

Purpose:

To characterize dark adaptation in patients with pseudoxanthoma elasticum, a systemic disease leading to calcification of elastic tissue including the Bruch membrane.

Methods:

In this prospective case–control study, dark adaptation thresholds were measured using a Goldmann-Weekers dark adaptometer. Additional assessments included best-corrected visual acuity testing, contrast sensitivity, low luminance deficit, and vision-related quality of life.

Results:

Dark adaptation thresholds were significantly higher, and adaptation periods were prolonged in patients with pseudoxanthoma elasticum (n = 35; 33 with 2 ABCC6 mutations) compared with controls (n = 35). The time to adapt 4 log units (20.6 ± 8.6 vs. 8.0 ± 1.3 minutes) and the mean dark adaptation threshold after 15 minutes (3.5 ± 1.1 vs. 1.8 ± 0.2 log units) were significantly different between patients and controls (both P < 0.001). Low luminance deficits (12.3 ± 6.4 vs. 6.1 ± 4.3 ETDRS letters), contrast sensitivity (1.4 ± 0.3 vs. 1.9 ± 0.1), and low luminance-related quality of life (LLQ score: 1,286 ± 355 vs. 2,167 ± 68) were also significantly worse in patients with pseudoxanthoma elasticum (all, P < 0.001). Two patients were treated with high-dose vitamin A which partially reversed impaired dark adaptation.

Conclusion:

Patients with pseudoxanthoma elasticum often have impaired dark adaptation. Positive effects of vitamin A supplementation may indicate restricted retinal access of vitamin A through the Bruch membrane as one possible underlying pathogenic factor.
DEVELOPMENT OF MACULAR ATROPHY AFTER PARS PLANA VITRECTOMY FOR MYOPIC TRACTION MACULOPATHY AND MACULAR HOLE RETINAL DETACHMENT IN PATHOLOGIC MYOPIA
Authors: Fang Yuxin , Yokoi Tae , Shimada Noriaki , Du Ran , Shinohara Kosei , Takahashi Hiroyuki , Uramoto Kengo , Ohno-Matsui Kyoko
Published: December 2019

Purpose:

To determine the incidence and long-term outcome of macular atrophy (MA) after pars plana vitrectomy (PPV) in pathologic myopia.

Methods:

Highly myopic patients who underwent PPV for myopic traction maculopathy and macular hole retinal detachment at Tokyo Medical and Dental University between 2012 and 2016 were studied. Fundus photographs and/or optical coherence tomography were examined before and after PPV at every visit.

Results:

A total of 133 eyes were followed for 39 months with the mean age of 62.8 years and the mean axial length of 30.0 mm. Postoperatively, 14 eyes (10.5%) developed fovea-centered MA, observed initially as a small, isolated, whitish lesion at the center of fovea at 3.5 months after PPV. The appearance of the MA was distinctly different from the choroidal neovascularization–related MA or patchy atrophy–related MA. With time, the lesions enlarged circumferentially. In these 14 eyes, the final best-corrected visual acuity was worse than the baseline, although the difference was not significant. The occurrence of MA was significantly associated with the preoperative foveal status.

Conclusion:

The development of MA can occur in 11% of highly myopic eyes after PPV for myopic traction maculopathy and macular hole retinal detachment. This postoperative MA might be a new complication of pathologic myopia.
Stroke Templates and Trainee Education are Associated With Improved Data Capture in an Academic Hospital
Authors: Toumbs Randi , Dao Thanh , Zhu Liang , McCullough Louise , Savitz Sean , Cossey TC
Published: December 2019

Background:

Effective medical record documentation is required to support accurate capture of diagnoses, patient acuity (case mix index [CMI]), and justify resource utilization for reimbursement. Billing code complexity and a lack of formal documentation education in training programs have created a need for academic medical centers to incorporate training for trainees (residents, fellows, and new nurse practitioners). We hypothesized that standardized stroke note templates, trainee education, and feedback from chart audits would improve documentation accuracy.

Purpose:

To improve the accurate/complete capture of expected (E) length of stay (LOS) and CMI by designing/implementing ischemic and hemorrhagic stroke templates containing high-frequency complication and comorbidity diagnoses with the greatest impact on stroke populations, combined with trainee education and chart audits.

Methods:

Descriptive statistics were used for outcomes before/after implementation of the templates. Primary outcomes include ELOS and CMI. Wilcoxon rank-sum test or chi-square test was used for group comparison.

Results:

The post-template group demonstrated a significant improvement in ELOS from 5.84 to 8.27 days (p < .0001). Case mix index increased (1.73–1.75; p < .0001) in the post-template group.

Conclusions:

Stroke-specific templates, trainee education, and chart audits were associated with significant improvement in documentation accuracy and an improved business model of stroke care in our hospital.
Leadership Competencies for Physical Therapists: A Delphi Determination
Authors: Sebelski Chris A , Green-Wilson Jennifer , Zeigler Stacey , Clark Diane , Tschoepe Barbara
Published: December 2019

Introduction.

Leadership is linked to patient experience and quality of care. Some health care professions have identified leadership competencies to guide curriculum design. Yet, the physical therapy profession lacks explicit leadership competencies for the point-of-care professional. The academic community is inconsistent including leadership development within Doctor of Physical Therapy entry-level education or residency/fellowship training. This project aimed to fill this knowledge gap and inform the conversation on leadership competencies essential for new graduate physical therapists while clarifying whether expectations differ for those physical therapists with additional experience who do not hold formal leadership positions.

Subjects.

Delphi panel of physical therapists with content expertise in leadership

Methods.

A collated document of leadership competencies was circulated electronically to the Delphi panelists for 2 rounds of structured review. Each panelist rated each competency for level of importance for new graduate physical therapists and the more experienced physical therapists. Consensus threshold was set priori at 0.80.

Results.

The Delphi panel consisted of 14 content experts. Ten completed 2 rounds of review. Of the 76 potential leadership competencies, 37 were deemed as “very important” and 1 as “somewhat” important for all physical therapists regardless of years postlicensure. Three were “not important” for new graduate physical therapists. Consensus was not reached on 35 leadership competencies.

Conclusions.

Identification of leadership competencies for physical therapists is essential for role identity and to impact quality of care and the overall patient experience in physical therapy. Results of this paper provide a foundation for discussions on the adoption of a set of leadership competencies within the profession to guide leadership development within curricula for entry-level and professional development activities.
Impact of DPT Student Coordination of a Physical Therapy Pro Bono Clinic: A Qualitative Investigation
Authors: Stickler Laurie , Hoogenboom Barbara J. , Ozga Karen
Published: December 2019

Introduction.

Pro bono physical therapy clinics provide a beneficial service to the community. Studies have identified a positive impact of student volunteerism in pro bono clinics. However, little is known about the immediate and long-term impact on those who serve as student coordinators of such clinics. Thus, the purpose of this study was to explore current and past pro bono clinic coordinators' perceptions of the professional and personal impact of serving as leaders of a pro bono physical therapy clinic.

Methods.

Current and past coordinators were recruited to participate in focus groups and individual interviews, respectively. All interviews were voice recorded, and the 4-step method for analyzing phenomenological data as described by Giorgi was used for data analysis.

Results.

Nine past coordinators agreed to participate in individual phone interviews, and 2 focus groups were conducted with a total of 8 current student coordinators. Three main themes emerged from the data: Essential Skills and Behaviors, Professional Development, and Personal Development.

Discussion and Conclusion.

Serving as a pro bono coordinator was an eye-opening multidimensional experience that transformed students on personal and professional levels. The results of this paper provide support for the development of leadership characteristics through participation as a student coordinator of a pro bono clinic. Such characteristics are highly desirable in the physical therapy profession.
The Image Fusion Technique for Cochlear Implant Imaging: A Study of its Application for Different Electrode Arrays
Authors: Sipari Sini , Iso-Mustajärvi Matti , Könönen Mervi , Löppönen Heikki , Dietz Aarno
Published: December 2019

Objectives:

To investigate the benefits of the image fusion technique for precise postoperative assessment of intracochlear placement with six different electrode arrays.

Study Design:

Consecutive retrospective case study.

Settings:

Tertiary referral center.

Patients:

Analyses of imaging data of 30 patients implanted with six different electrode arrays.

Interventions:

Electrode reconstructions obtained from postoperative cone-beam computed tomography (CBCT) were overlaid onto preoperative magnetic resonance imaging (MRI) and/or high-resolution computed tomography (HRCT) registrations to create artefact-free images.

Main Outcome Measures:

Each electrode's intracochlear position was analyzed with the image fusion reconstructions and compared with the results obtained by CBCT alone. The electrode location was classified according to its position in relation to the basal membrane at four different insertion angles.

Results:

In 40 out of 151 measurements (26.5%), the location grading obtained by CBCT alone changed after the assessment with the image fusion reconstructions. A significant association was found between deep insertions (over 360 degrees) and the effectiveness of image fusion (p = 0.019). The difference between the impact of the fusion technique for the basal turn versus the apical part was highly significant (p = 0.001). There was no significant difference between the effectiveness of the image fusion and the different electrodes.

Conclusions:

By utilizing an image fusion technique, a more accurate assessment of electrode placement could be achieved for all types of electrodes. Image fusion was especially beneficial for insertions beyond 360 degrees.
Transplantation in older individuals: is it really better than dialysis?
Authors: Hellemans Rachel , Jager Kitty J. , Abramowicz Daniel
Published: December 2019

Purpose of review

The kidney transplantation landscape has changed dramatically over the last 2 decades. First, transplantation is performed in patients previously considered ineligible for transplantation, including older patients and patients with multiple comorbidities. Second, organ shortages have increased the use of less-than-optimal donor kidneys, like organs from expanded criteria donors or donors after cardiac death. Third, improvements in managing chronic kidney disease and dialysis have improved survival on dialysis. Therefore, the question arises: does transplantation currently benefit older transplant candidates?

Recent findings

The current review describes important changes in transplantation over the last 20 years. We review recent data on survival with dialysis versus transplantation in older individuals. Finally, we consider methodological issues that might influence conclusions drawn in current studies.

Limited data are available to assess the potential survival benefit of kidney transplantations in older individuals. The available evidence suggests that transplantation might provide survival benefit in older individuals, even with aged kidney donors, but risks vary widely with donor quality and recipient health status. More research is needed to make adequate predictions of which donor kidneys might lead to good outcomes and which patient characteristics might define a good transplant candidate.
Herbidospora galbida sp. nov., a novel actinobacterium isolated from soil
Authors: Han Liyuan , Yu Mingying , Zhao Junwei , Jiang Hao , Guo Xiaowei , Shen Guijin , Shen Yue , Wang Xiangjing , Xiang Wensheng
Published: December 2019

A novel actinobacterium, designated strain NEAU-GS14T, was isolated from soil of a flower bed in a residential area in Sanya, Hainan Province, China, and characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics of the strain coincided with members of the genus Herbidospora. The 16S rRNA gene sequence analysis showed that strain NEAU-GS14T belongs to the genus

Herbidospora

and was most closely related to

Herbidospora daliensis

JCM 18061T (98.8 %), other type strains of species of the genus

Herbidospora

were found to be less than 98.7 %. Phylogenetic analysis using the 16S rRNA gene sequences showed that the strain formed a cluster with

Herbidospora daliensis

JCM 18061T. Cell wall contained meso-diaminopimelic acid as the major diamino acid and the whole-cell hydrolysates were glucose, madurose and ribose. The major polar lipids were diphosphatidylglycerol, hydroxyphosphatidylethanolamine, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphoglycolipids and two phosphatidylinositol mannosides. The predominant menaquinone was MK-10(H4). Major fatty acids were 10-methly C17 : 0 and C17 : 0, these chemotaxonomic data supported the affiliation of strain NEAU-GS14T to the genus

Herbidospora

. The DNA G+C content was 70.6 mol%. Furthermore, the strain could be clearly distinguished by digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) values and some phenotypic characteristics. Therefore, it is proposed that strain NEAU-GS14T represents a novel species of the genus

Herbidospora

, for which the name Herbidospora galbida sp. nov. is proposed. The type strain is NEAU-GS14T (=CCTCC AA 2018040T=JCM 33459T).
Genetic analysis of functional rare germline variants across 9 cancer types from the DiscovEHR study
Authors: Shivakumar Manu , Miller Jason E. , Dasari Venkata Ramesh , Carey David , Gogoi Radhika , Kim Dokyoon
Published: December 2019

Rare variants play an essential role in the etiology of cancer and characterizing rare germline variants that impact the risk of cancer is an ongoing challenge. We performed a genome-wide rare variant analysis using germline whole exome sequencing (WES) data derived from the Geisinger MyCode initiative to discover cancer predisposition variants. The case-control association analysis was conducted by binning pathogenic and likely pathogenic variants in 5,538 cancer patients and 7,286 matched controls in a discovery set and 1,991 cancer patients and 2,504 matched controls in a validation set across nine cancer types. We discovered 87 genes and 106 pathways significantly associated with cancer (Bonferroni-corrected P< 0.05) out of which seven genes and 26 pathways replicated from the validation set (suggestive threshold P< 0.05). Further, four genes and 21 pathways were discovered to be associated with multiple cancers (Bonferroni-corrected P< 0.05). Additionally, we identified 13 genes and two pathways associated with survival outcome across seven cancers (Bonferroni-corrected P< 0.05), where two genes,PCDHB8andDCHS2, were also associated with survival outcome in TCGA data. In summary, we conducted one of the largest pan-cancer association studies using germline data derived from a single hospital system to find novel predisposition genes and pathways associated with nine cancers. Our results can inform future guidelines for germline genetic testing in cancer, which will be helpful in screening for cancer high-risk patients. This work adds to the knowledge base and progress being made in precision medicine.
The genetic basis of sex determination in grapevines (Vitis spp.)
Authors: Massonnet Mélanie , Cochetel Noé , Minio Andrea , Vondras Amanda M. , Muyle Aline , Lin Jerry , Garcia Jadran F. , Zhou Yongfeng , Delledonne Massimo , Riaz Summaira , Figueroa-Balderas Rosa , Gaut Brandon S. , Cantu Dario
Published: December 2019

Sex determination in grapevine evolved through a complex succession of switches in sexual systems. Phased genomes built with single molecule real-time sequencing reads were assembled for eleven accessions of cultivated hermaphrodite grapevines and dioecious males and females, including the ancestor of domesticated grapevine and other related wild species. By comparing the phased sex haplotypes, we defined the sex locus of theVitisgenus and identified polymorphisms spanning regulatory and coding sequences that are in perfect association with each sex-type throughout the genus. These findings identified a novel male-fertility candidate gene,INP1, and significantly refined the model of sex determination inVitisand its evolution.
Chromosome-scale genome assembly provides insights into rye biology, evolution, and agronomic potential
Authors: Rabanus-Wallace M. Timothy , Hackauf Bernd , Mascher Martin , Lux Thomas , Wicker Thomas , Gundlach Heidrun , Báez Mariana , Houben Andreas , Mayer Klaus F.X. , Guo Liangliang , Poland Jesse , Pozniak Curtis J. , Walkowiak Sean , Melonek Joanna , Praz Coraline , Schreiber Mona , Budak Hikmet , Heuberger Matthias , Steuernagel Burkhard , Wulff Brande , Börner Andreas , Byrns Brook , Čížková Jana , Fowler D. Brian , Fritz Allan , Himmelbach Axel , Kaithakottil Gemy , Keilwagen Jens , Keller Beat , Konkin David , Larsen Jamie , Li Qiang , Myśków Beata , Padmarasu Sudharsan , Rawat Nidhi , Sesiz Uğur , Sezgi Biyiklioglu , Sharpe Andy , Šimková Hana , Small Ian , Swarbreck David , Toegelová Helena , Tsvetkova Natalia , Voylokov Anatoly V. , Vrána Jan , Bauer Eva , Bolibok-Bragoszewska Hanna , Doležel Jaroslav , Hall Anthony , Jia Jizeng , Korzun Viktor , Laroche André , Ma Xue-Feng , Ordon Frank , Özkan Hakan , Rakoczy-Trojanowska Monika , Scholz Uwe , Schulman Alan H. , Siekmann Dörthe , Stojałowski Stefan , Tiwari Vijay , Spannagl Manuel , Stein Nils
Published: December 2019

We present a chromosome-scale annotated assembly of the rye (Secale cerealeL. inbred line ‘Lo7’) genome, which we use to explore Triticeae genomic evolution, and rye’s superior disease and stress tolerance. The rye genome shares chromosome-level organization with other Triticeae cereals, but exhibits unique retrotransposon dynamics and structural features. Crop improvement in rye, as well as in wheat and triticale, will profit from investigations of rye gene families implicated in pathogen resistance, low temperature tolerance, and fertility control systems for hybrid breeding. We show that rye introgressions in wheat breeding panels can be characterised in high-throughput to predict the yield effects and trade-offs of rye chromatin.
Targeting the Long Non-Coding RNA LINC00599-205 splicing by novel candidate drug ABX464 to produce the anti-inflammatory microRNA miR-124
Authors: Manchon Laurent , Vautrin Audrey , Tazi Jamal , Garcel Aude , Campos Noelie
Published: December 2019

Many nascent long non-coding RNAs have received considerable attention in recent years because of their major regulatory roles in gene expression and signaling pathways at various levels. Indeed long non-coding RNAs undergo the same maturation steps as pre-mRNAs of proteincoding genes, but they are less efficiently spliced and polyadenylated in comparison to them. Here we focus on a specific human long non-coding RNA and we show the activity of a new candidate drug that potentially affect its splicing and generate an anti-HIV and anti-inflammatory effects driven by upregulation of microRNA biogenesis. To investigate this activity we combine the use of capture sequencing technology and anab initiotranscript assembly on cells from six healthy individuals. The sequencing depth of capture sequencing permitted us to assemble transcripts exhibiting a complex array of splicing patterns. In essence, we revealed that splicing of the long non-coding RNA is activated by the drug whereas this splicing was not present in untreated samples.
Early sexual dimorphism in the developing gut microbiome of northern elephant seals
Authors: Stoffel M.A. , Acevedo-Whitehouse K. , Morales-Durán Nami , Grosser S. , Chakarov. N. , Krüger O. , Nichols H.J. , Elorriaga-Verplancken F.R. , Hoffman J.I.
Published: December 2019

The gut microbiome is an integral part of a species’ ecology, but we know little about how host characteristics impact its development in wild populations. Here, we explored the role of such intrinsic factors in shaping the gut microbiome of northern elephant seals during a critical developmental window of six weeks after weaning, when the pups stay ashore without feeding. We show that the early-life gut microbiome is already substantially different in male and female pups, even though males and females cannot yet be distinguished morphologically. Sex and age both explain around 15% of the variation in gut microbial beta diversity, while microbial communities sampled from the same individual show high levels of similarity across time, explaining another 40% of the variation. Only a small proportion of the variation in beta diversity is explained by health status, but healthy individuals have a greater microbial alpha diversity than their non-healthy peers. Across the post-weaning period, the elephant seal gut microbiome is highly dynamic. We found evidence for several colonisation and extinction events as well as a decline inBacteriodesand an increase inPrevotella, a pattern that has previously been associated with the transition from nursing to solid food. Lastly, we show that genetic relatedness is correlated with gut microbiome similarity in males but not females, again reflecting substantial early sex-differences. Our study represents a naturally diet-controlled and longitudinal investigation of how intrinsic factors shape the early gut microbiome in a species with extreme sex differences in morphology and life history.
Predicting Geographic Location from Genetic Variation with Deep Neural Networks
Authors: Battey C.J. , Ralph Peter L. , Kern Andrew D.
Published: December 2019

Most organisms are more closely related to nearby than distant members of their species, creating spatial autocorrelations in genetic data. This allows us to predict the location of origin of a genetic sample by comparing it to a set of samples of known geographic origin. Here we describe a deep learning method, which we callLocator, to accomplish this task faster and more accurately than existing approaches. In simulations,Locatorinfers sample location to within 4.1 generations of dispersal and runs at least an order of magnitude faster than a recent model-based approach. We leverageLocator’s computational efficiency to predict locations separately in windows across the genome, which allows us to both quantify uncertainty and describe the mosaic ancestry and patterns of geographic mixing that characterize many populations. Applied to whole-genome sequence data fromPlasmodiumparasites,Anophelesmosquitoes, and global human populations, this approach yields median test errors of 16.9km, 5.7km, and 85km, respectively.
Tracking attention in a visual active paradigm for the diagnosis of disorders of consciousness
Authors: Lesenfants Damien , Chatelle Camille , Laureys Steven , Noirhomme Quentin
Published: December 2019

Abstract

Background

Clinical assessment of patients with disorders of consciousness (DOC) relies on the clinician’s ability to detect a behavioral response to an instruction (e.g., “squeeze my hand”). However, recent studies have shown that some of these patients can produce volitional brain responses to command while no behavioral response is present. This highlights the importance of developing motor-independent diagnostic tool for this population, complementing standardized behavioral evaluation. We here evaluate the ability of a novel gaze-independent attention-based EEG paradigm to detect volitional attentional processes in patients with disorders of consciousness.

Methods

Thirty patients with DOC were included in the study: 12 with an unresponsive wakefulness syndrome, 16 in a minimally conscious state (MCS), two who emerged from a MCS. Patients were randomly instructed to either concentrate on a task or rest while brain activity was recorded using EEG during a gaze-independent paradigm.

Results

One of two EMCS, one of 16 MCS and one of 12 UWS patients showed a response to command using the attention task. Interestingly, this method could detect a brain-based response to command in one MCS patient who did not present a behavioral response to command at the bedside the day of the assessment.

Conclusion

This study show that task-related variation of attention during an active task could help to objectively detect response to command in patients with DOC.
Reward value revealed by auction in rhesus monkeys
Authors: Al-Mohammad Alaa , Schultz Wolfram
Published: December 2019

Economic choice is thought to involve the elicitation of the subjective values of the choice options. Thus far, value estimation in animals has relied upon stochastic choices between multiple options presented in repeated trials and expressed from averages of dozens of trials. However, subjective reward valuations are made moment-to-moment and do not always require alternative options; their consequences are usually felt immediately. Here we describe a Becker-DeGroot-Marschak (BDM) auction-like mechanism that provides more direct and simple valuations with immediate consequences. The BDM encourages agents to truthfully reveal their true subjective value in individual choices (’incentive compatibility’). Monkeys reliably placed well-ranked BDM bids for up to five juice volumes while paying from a water budget. The bids closely approximated the average subjective values estimated with conventional binary choices, thus demonstrating procedural invariance and aligning with the wealth of knowledge acquired with these less direct estimation methods. The feasibility of BDM bidding in monkeys paves the way for an analysis of subjective neuronal value signals in single trials rather than from averages; the feasibility also bridges the gap to the increasingly used BDM method in human neuroeconomics.

Significance

The subjective economic value of rewards cannot be measured directly but must be inferred from observable behavior. Until now, the estimation method in animals was rather complex and required comparison between several choice options during repeated choices; thus, such methods did not respect the imminence of the outcome from individual choices. However, human economic research has developed a simple auction-like procedure that can reveal in a direct and immediate manner the true subjective value in individual choices (Becker-DeGroot-Marschak, BDM, mechanism). The current study implemented this mechanism in rhesus monkeys and demonstrates its usefulness for eliciting meaningful value estimates of liquid rewards. The mechanism allows future neurophysiological assessment of subjective reward value signals in single trials of controlled animal tasks.
Combined salinity and acidity stressors alterDaphnia magnapopulation growth and structure under severe absence of photoperiod
Authors: Khudr Mouhammad Shadi , Purkiss Samuel Alexander , Hager Reinmar
Published: December 2019

Although natural and anthropogenic influences affect freshwater ecosystems globally at unprecedented levels, the effects of co-occurring physico-chemical stress on zooplankton phenotypic plasticity under extreme conditions remain understudied.

We exposed a laboratory-raised clonal population ofDaphnia magnato different stress levels of acidity and salinity undergoing complete constant light over 30 days. Overall, population size and age structure at day 10 considerably differed between specific stress contexts. All populations expanded compared to the starting population on day 1. On day 30, overall, population size increased but showed significant differences between treatment groups. Surprisingly,Daphniaperformed better under combined stress of salinity and acidity than under acidity alone as the extra salinity in the medium may have counterbalanced sodium loss caused by lower pH. Our results reveal a considerable degree of differential reproductive and ontogenetic plasticity in response to combined stressors under disrupted photoperiod. Exposure to constant light led to increased population size, which may be a result of supercharged ion regulation that enables zooplankton to survive better under specific levels of extreme environmental change and adverse chemical stress. Our findings merit further molecular investigation of phenotypic plasticity of the congeners across severe combined stress conditions.
The effect of left fronto-parietal resections on hand selection: a lesion-tractography study
Authors: Howells Henrietta , Puglisi Guglielmo , Leonetti Antonella , Vigano Luca , Fornia Luca , Simone Luciano , Forkel Stephanie J. , Rossi Marco , Riva Marco , Cerri Gabriella , Bello Lorenzo
Published: December 2019

Strong right-hand preference on the population level is a uniquely human feature, although the neural basis for this is still not clearly defined. Recent behavioural and neuroimaging literature suggests that hand preference may be related to the orchestrated function and size of fronto-parietal white matter tracts bilaterally. Lesions to these tracts induced during tumour resection may provide an opportunity to test this hypothesis. In the present study, a cohort of seventeen neurosurgical patients with left hemisphere brain tumours were recruited to investigate whether resection of certain white matter tracts affects the choice of hand selected for the execution of a goal-directed task (assembly of jigsaw puzzles). Patients performed the puzzles, but also tests for basic motor ability, selective attention and visuo-constructional ability, preoperatively and one month after surgery. Diffusion tractography of fronto-parietal tracts (the superior longitudinal fasciculus) and the corticospinal tract were performed, to evaluate whether resection of tracts was significantly associated with changes in hand selection. A complementary atlas-based disconnectome analysis was also conducted. Results showed a shift in hand selection despite the absence of any motor or cognitive deficits, which was significantly associated with patients with frontal and parietal resections, compared with those with resections in other lobes. In particular, this effect was significantly associated with the resection of dorsal fronto-parietal white matter connections, but not with the ventral fronto-parietal tract. Dorsal white matter pathways contribute bilaterally, with specific lateralised competencies, to control of goal-directed hand movements. We show that unilateral lesions, by unbalancing the cooperation of the two hemispheres, can alter the choice of hand selected to accomplish movements.
Lactobacillus reuteri: direct passage from ingested yogurts to urine microbiota
Authors: Lagier Jean-Christophe , Mekhalif Fatima , Merhej Vicky , Chaudet Hervé , Delerce Jérémy , Levasseur Anthony , Raoult Didier
Published: December 2019

Background

Serendipitously, it was observed that fecal transplantation made forClostridium difficilemay cure chronic urinary tract infections. This led us to evaluate the passage in the urine of probiotics contained in yoghurt, which have been claimed to prevent urinary infections.

Results

A commercial yogurt that contained 3 probiotics (Bifidobacterium animalis, Lactobacillus delbrueckiiiandLactobacillus reuteri) was consumed by 28 healthy subjects. We performed by culturomics, urine analysis before and after feeding these yogurts. Genome sequencing of the bacterial strains absent before yogurt consumption and present after consumption was performed. Testing more than 40,000 colonies by MALDI-TOF, we observed in two men and one woman (11% of subjects included), the urine colonization of the sameLactobacillus reuteripresent in yogurts, with the same genome with 50 genes never identified in other lactobacilli.

Conclusion

This confirms that, as ingested,Lactobacillus salivariuspasses into the milk of lactating women, some bacteria, particularlyLactobacilluscan colonize body fluids previously considered sterile after ingestion via the digestive route. Although the consequences of this passage remain unknown, we prove for the first time that there is a digestive passage in the urine after consumption of probiotics, including fermented products sold commercially.
Helping those who help others for indirect fitness benefits not indirect reciprocity
Authors: Roberts Gilbert
Published: December 2019

Helping those who help others appears to be a widespread phenomenon. It is typically framed as indirect reciprocity in which individuals who are seen to help later receive returns from third parties. However, indirect reciprocity only works when individuals condition their help not just on how their recipient has behaved in the past but also on whether their recipient was justified in behaving that way. It also requires sufficient repeated interactions of this type among other individuals for a benefit to be reciprocated. These factors limit the scope of indirect reciprocity to explain cases where people do help those who help others. Here, I propose instead that helping can be explained by the indirect fitness benefits (or ‘relatedness’) that result from helping other helpers in groups. This means that when individuals help other helpers, they may not make any returns via indirect reciprocity, but rather they may be helping a strategy of helping those who help. In this way, the helping strategy can spread even when helping has no net benefit to the individual helper. This is a form of relatedness in which individuals help their kin that are recognized by their helping behaviour. As such, conditional helping is likely to be found where population structure promotes relatedness through non-random association. The analysis suggests indirect reciprocity may not have played the decisive role in the evolution of human cooperation that is often thought, but paradoxically that the use of image scores deserves renewed attention as a strategy of helping those with the same behaviour.