bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of physiotherapy in childhood functional constipation: a randomized controlled trial in primary care
Authors: van Summeren Jojanneke J G T , Holtman Gea A , Lisman-van Leeuwen Yvonne , van Ulsen-Rust Alice H C , Vermeulen Karin M , Tabbers Merit M , Kollen Boudewijn J , Dekker Janny H , Berger Marjolein Y
Published: November 2021

Objective

Health care expenditures for children with functional constipation (FC) are high, while conservative management is successful in only 50% of the children. The aim is to evaluate whether adding physiotherapy to conventional treatment (CT) is a cost-effective strategy in the management of children with FC aged 4–18 years in primary care.

Methods

A cost-effectiveness analysis was performed alongside a randomized controlled trial (RCT) with 8-month follow-up. Costs were assessed from a societal perspective, effectiveness included both the primary outcome (treatment success defined as the absence of FC and no laxative use) and the secondary outcome (absence of FC irrespective of laxative use). Uncertainty was assessed by bootstrapping and cost-effectiveness acceptability curves (CEACs) were displayed.

Results

One hundred and thirty-four children were randomized. The incremental cost-effectiveness ratio (ICER) for one additional successfully treated child in the physiotherapy group compared with the CT group was €24,060 (95% confidence interval [CI] €−16,275 to €31,390) and for the secondary outcome €1,221 (95% CI €−12,905 to €10,956). Subgroup analyses showed that for children with chronic laxative use the ICER was €2,134 (95% CI −24,975 to 17,192) and €571 (95% CI 11 to 3,566), respectively. At a value of €1,000, the CEAC showed a probability of 0.53 of cost-effectiveness for the primary outcome, and 0.90 for the secondary outcome.

Conclusions

Physiotherapy added to CT as first-line treatment for all children with FC is not cost-effective compared with CT alone. Future studies should consider the cost-effectiveness of physiotherapy added to CT in children with chronic laxative use.

Trial registration

The RCT is registered in the Netherlands Trial Register (NTR4797), on the 8th of September 2014. The first child was enrolled on the 2nd of December 2014. https://www.trialregister.nl/trial/4654.
Couples’ Experiences Managing Young-Onset Dementia Early in the COVID-19 Pandemic
Authors: Bannon Sarah M , Wang Katherine E , Grunberg Victoria A , Dickerson Bradford C , Vranceanu Ana-Maria
Published: November 2021

Background and Objectives

The coronavirus disease 2019 (COVID-19) pandemic created unexpected stressors for society and could disproportionately affect more vulnerable groups. One such group is couples facing young-onset dementias (YOD), who experience pandemic-induced stressors alongside ongoing YOD-related stressors (e.g., progressive symptoms, increased caregiving needs). Using a qualitative design, our objective was to characterize the experiences of couples living with YOD early in the COVID-19 pandemic and the impact on couples’ ‘relationships’ and well-being.

Research Design and Methods

Couples (N = 23) of persons with YOD and their spousal caregivers participated in a 1 hour live video, joint interview during the early COVID-19 pandemic. We used a hybrid inductive–deductive coding approach to thematic analysis to extract findings within 2 a priori domains: (a) psychosocial stressors experienced during the early pandemic and (2) the impact of early pandemic stressors on couples’ relationships and well-being.

Results

Thematic analyses revealed 6 main themes: (a) increased caregiving responsibilities, (b) increased uncertainty, (c) increased social isolation and disruptions in social support and medical care, (d) loss of meaningful activities and routines, (e) changes to the couple’s relationship, and (f) heightened emotional distress.

Discussion and Implications

The COVID-19 pandemic exacerbated relationship strain and distress among couples managing YOD. This population may face negative outcomes due to the dual impact of YOD- and pandemic-related stressors. It is imperative to provide timely resources and psychosocial support to couples facing YOD to mitigate the negative impact of such stressors on individual health and well-being and the couples’ relationship together.
Neutrophil Extracellular Trap Density Increases With Increasing Histopathological Severity of Crohn’s Disease
Authors: Schroder Angie L , Chami Belal , Liu Yuyang , Doyle Chloe M , El Kazzi Mary , Ahlenstiel Golo , Ahmad Gulfam , Pathma-Nathan Nimalan , Collins Geoff , Toh James , Harman Andrew , Byrne Scott , Ctercteko Grahame , Witting Paul K
Published: November 2021

Background

Intestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans.

Methods

Human intestinal biopsies were collected from Crohn’s disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score.

Results

A significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P < .0001) and unaffected CD (P < .0001), with transitional CD specimens also showing greater staining than controls (P < .05) and unaffected CD (P < .05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P < .0001) and unaffected CD (P < .0001) and was significantly higher in transitional CD than in controls (P < .0001) and unaffected CD (P < .0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P < .05), unaffected CD (P < .0001) and transitional CD (P < .05), with transitional CD specimens showing greater staining than unaffected CD (P < .01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment.

Conclusion

These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.
Effects of bone morphogenetic protein 4, gremlin, and connective tissue growth factor on estradiol and progesterone production by bovine granulosa cells
Authors: Spicer Leon J , Schutz Luis F , Aad Pauline Y
Published: November 2021

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β family of proteins that have been implicated in the paracrine regulation of granulosa cell (GC) function, but whether responses to BMPs change with follicular size or interact with connective tissue growth factor (CTGF) or BMP antagonists (e.g., gremlin [GREM]) to directly affect GC function of cattle is unknown. Therefore, to determine the effects of BMP4 on proliferation and steroidogenesis of GCs and its interaction with GREM or CTGF, experiments were conducted using bovine GC cultures. In vitro, BMP4 (30 ng/mL) inhibited (P < 0.05) follicle-stimulating hormone (FSH) plus insulin-like growth factor 1 (IGF1)-induced progesterone and estradiol production by large- and small-follicle GCs, but the inhibitory effect of BMP4 on estradiol production was much more pronounced in large-follicle GCs. In small-follicle GCs, BMP4 had no effect (P > 0.10) on IGF1-induced proliferation, but GREM inhibited (P < 0.05) cell proliferation and estradiol and progesterone production in IGF1 plus FSH-treated GCs. In large-follicle GCs, BMP4 (10 to 30 ng/mL) increased (P < 0.05) GC numbers and GREM (100 ng/mL) blocked this effect. In large-follicle GCs, CTGF inhibited (P < 0.05) FSH plus IGF1-induced progesterone and estradiol production, and CTGF blocked the stimulatory effect of BMP4 on GC proliferation. These results indicate that BMP4, GREM, and CTGF inhibit GC aromatase activity and progesterone production. Also, the stimulatory effect of BMP4 on GC proliferation and the inhibitory effects of BMP4 on GC steroidogenesis are more pronounced in large vs. small follicles.
A taxonomy of successful ageing conceptions
Authors: Tesch-Römer Clemens , Wahl Hans-Werner , Rattan Suresh I. S. , Ayalon Liat
Published: November 2021

The authors propose a taxonomy of successful ageing conceptions organized according to five selected models of successful ageing used in ageing research. The models are rooted—explicitly or implicitly—in philosophical traditions describing a good life. The dominant model in gerontological research, Rowe and Kahn’s model of successful ageing, follows the tradition of American pragmatism, emphasizing practical effects of concepts and ideas. In addition to this model, four additional models of successful ageing are introduced and discussed: hedonic, eudaimonic, capability approach, and care ethics-based, each of them coming from different philosophical schools. The five models are compared according to the following criteria: age relevance, inclusiveness, locus of responsibility, normativity, and measurability. The taxonomy lies the ground for all the arguments that follow in the remainder of the book.
Towards a new narrative on successful ageing
Authors: Tesch-Römer Clemens , Wahl Hans-Werner , Rattan Suresh I. S. , Ayalon Liat
Published: November 2021

The major task of this closing chapter is to strive for reconciliation between the very divergent positions and perspectives on successful ageing that have been outlined in this book. The building blocks enabling at least partial reconciliation are the emphasis of the need for pluralism in conceptual reasoning on the notion of successful ageing; the insistence that one must be aware of the full implications of choosing any particular model of successful ageing; and the claim that the discourse on successful ageing can only, to a limited extent, be driven by empirical data. Instead, illuminating the underlying normative conceptions of what it means to enjoy a good life in old age is key to arrive at a more holistic picture of successful ageing that comes with heuristic utility. At the same time, visions of the good life in old age need further elaboration, but remaining ambivalences seem unavoidable.
The skull base
Authors: van Gijn Daniel R. , Dunne Jonathan
Published: November 2021

The skull base is a complex amalgamation of bones and their respective fossae, foramina and fissures and of multiple surgical specialties – blurring the boundaries between ENT surgeons, plastic surgeons, neurosurgeons, radiologists and oral and maxillofacial surgeons. This rough terrain is an area much loved by examiners and anatomists, and conversely (and universally) feared by students. The skull base divides the neurocranium from the viscerocranium and can be considered as having a superior (intracranial) surface and an inferior (extracranial) surface, the cranial base.
The salivary glands
Authors: van Gijn Daniel R. , Dunne Jonathan
Published: November 2021

There are three paired major salivary glands of the head and neck, all named according to their location and each contributing to saliva and enzyme production via their respective ducts to assist with mastication and digestion. At rest, the lion’s share (60%) of saliva production is from the submandibular glands. On stimulation, the parotid contribution increases from 20% to 50%. There are up to 1000 minor salivary glands found within the submucosa of the oral cavity – 1-2mm in size and predominantly mucous in nature. The parotid glands are irregular shaped masses of lobulated tissue situated on the side of the face, reaching from the zygomatic arch superiorly to the upper part of the neck inferiorly where they overly the posterior belly of digastric and upper sternocleidomastoid muscle. Anteriorly, the gland lies between the posterior border of the mandibular ramus before continuing below the external acoustic meatus towards the mastoid process posteriorly.
Management of the sick child
Authors: Molyneux Elizabeth , O’Hare Bernadette
Published: November 2021

Emergency triage assessment, Management of shock in children with severe malnutrition, Coma and convulsions, The sick young infant, Neonatal notes, Low birth weight and prematurity, Perinatal asphyxia/hypoxic ischaemic encephalopathy, Neonatal infection
Poisoning and envenoming
Authors: Eddleston Michael , Warrell David
Published: November 2021

Acute poisoning?, Acute pesticide poisoning?, Organophosphates/carbamates?, Acute poisoning with pharmaceuticals/chemicals?, Mushroom poisoning?, Methanol poisoning?, Fish and shellfish poisoning?, Snake bite?, Scorpion sting?, Spider bite?, Fish stings?, Jelly fish stings?
Health emergencies in humanitarian crises
Authors: Ritmeijer Koert
Published: November 2021

Initial assessment?, Measles immunization?, Water and sanitation?, Food and nutrition?, Shelter and site planning?, Basic healthcare?, Control of communicable diseases and epidemics?, Public health surveillance?, Human resources coordination and managment?, Post-emergency phase?
Healthcare-associated infection, antimicrobial prescribing, and antimicrobial resistance
Authors: Stoesser Nicole
Published: November 2021

Healthcare-associated infection, Principles of antimicrobial prescribing, Antimicrobial resistance
New Insights About Military Interprofessional Healthcare Teams: Lessons Learned and New Directions From a Program of Research
Authors: Varpio Lara , Bader-Larsen Karlen S , Hamwey Meghan K , Meyer Holly S , Artino Anthony , Cruthirds Danette F , Durning Steven J
Published: November 2021

The success of the military is significantly supported by highly effective collaborative teams. While much is known about successful military teams outside the context of healthcare delivery, considerably less attention has been paid to teams working in patient care. Thus, this supplement has explored the features of successful military interprofessional healthcare teams (MIHTs). In this summary paper, the authors discuss what this supplement’s investigations have taught us about MIHTs and offer a series of proposed future investigations of MIHTs and their role in military healthcare.
Military Interprofessional Healthcare Teams: Identifying the Characteristics That Support Success
Authors: Varpio Lara , Bader-Larsen Karlen S , Durning Steven J , Artino Anthony , Hamwey Meghan K , Cruthirds Danette F , Meyer Holly S
Published: November 2021

Military interprofessional healthcare teams (MIHTs) are foundational to the care provided to military members and their families. However, to date, very little research has investigated MIHTs. Notably, we have few insights into what distinguishes successful MIHTs. This manuscript presents findings from a program of research that was carried out to address this gap. We review what is known about MIHTs to date and the Uniformed Services University’s (USU) focused efforts to ensure that greater understanding of MIHTs was developed. We provide an overview of the USU-supported research and of the findings that were generated by that inquiry. After summarizing the manuscripts included in this special edition of Military Medicine, we close by acknowledging and thanking key members of the U.S. military healthcare system who supported this research.
Knowledgeability and Identification: Explaining Military Interprofessional Healthcare Teams’ Excellence and Readiness
Authors: Stalmeijer Renée E
Published: November 2021

The importance of successful interprofessional collaboration for effective patient care is generally acknowledged. Research into interprofessional collaboration has thus far been mainly situated in the civilian context and has mostly indicated barriers that prevent successful interprofessional collaboration. However, military interprofessional healthcare teams (MIHTs) seem to be exceptionally successful. Building on the overarching finding of the studies within this special edition—i.e., that MIHTs’ readiness and excellence are in part due to healthcare professionals’ “shared understanding” of what is needed to effectively serve on an MIHT—this commentary uses the theory of Landscape of Practice as a lens to further explain the processes through which healthcare professionals attain this shared understanding. Used within the fields of Health Professions Education and workplace learning, Landscapes of Practice (LoP) helps to explain how learning occurs within practice. It highlights how, by engaging within the various working environments belonging to a profession, social interactions between the various professionals within that environment form the conduit for learning. LoP highlights that the outcome of this learning process is “knowledgeability,” i.e., understanding of how to engage within the field and with its players, resulting in being an acknowledged member of the field. Fostered through a process called “identification,” professionals learn to see how their professional practice aligns with that of others and how to effectively collaborate with others. The commentary explains how the findings of the separate studies within this special edition strongly resonate with knowledgeability and identification. It is concluded that civilian interprofessional healthcare teams may benefit from incorporating characteristics of MIHTs in their training programs.
Synthesis, crystal structure, and in vitro evaluation of the anticancer activity of new Pt (Pd) complexes with 1-[(dimethylamino)methyl]-2-naphthol ligand
Authors: Akhmetova Vnira R , Bikbulatova El'mira M , Mescheryakova Ekaterina S , Gil'manova Elina N , Dzhemileva Lilya U , D'yakonov Vladimir A
Published: November 2021

The synthesis of new Pt(II) and Pd(II) complexes with 1-aminomethyl-2-naphtol ligands has been first performed. The adducts of [PtCl4]2− and [PdCl4]2− anions with the 1-aminomethyl-2-naphtol NH cation were synthesized. The structure for four Pt (Pd)-containing compounds was investigated using X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat and K562 human leukemia cells, lymphoma U937cells, A2780 and the cisplatin-resistant A2780cis lines of human ovarian cancer, and normal fibroblasts. Study of induction of apoptosis and the effect of new palladium and platinum complexes on the cell cycle was carried out. The cells showed a higher sensitivity to Pt(II) compounds than to Pd(II) ones. All the synthesized metal complexes show much more antitumor activity compared with a platinum-containing cisplatin drug.
Prediction of conserved and variable heat and cold stress response in maize using cis-regulatory information
Authors: Zhou Peng , Enders Tara A , Myers Zachary A , Magnusson Erika , Crisp Peter A , Noshay Jaclyn M , Gomez-Cano Fabio , Liang Zhikai , Grotewold Erich , Greenham Kathleen , Springer Nathan M
Published: November 2021

Changes in gene expression are important for responses to abiotic stress. Transcriptome profiling of heat- or cold-stressed maize genotypes identifies many changes in transcript abundance. We used comparisons of expression responses in multiple genotypes to identify alleles with variable responses to heat or cold stress and to distinguish examples of cis- or trans-regulatory variation for stress-responsive expression changes. We used motifs enriched near the transcription start sites (TSSs) for thermal stress-responsive genes to develop predictive models of gene expression responses. Prediction accuracies can be improved by focusing only on motifs within unmethylated regions near the TSS and vary for genes with different dynamic responses to stress. Models trained on expression responses in a single genotype and promoter sequences provided lower performance when applied to other genotypes but this could be improved by using models trained on data from all three genotypes tested. The analysis of genes with cis-regulatory variation provides evidence for structural variants that result in presence/absence of transcription factor binding sites in creating variable responses. This study provides insights into cis-regulatory motifs for heat- and cold-responsive gene expression and defines a framework for developing models to predict expression responses across multiple genotypes.
Emergency Department Evaluation of Abdominal Pain in Adolescent Females
Authors: Lawrence Amy E. , Ervin Emma , Sebastião Yuri V. , Hewitt Geri , Minneci Peter C. , Deans Katherine J.
Published: November 2021

(Abstracted from J Pediatr Adolesc Gynecol 2021;34(5):649–655)

Abdominal pain is a very common chief complaint among adolescents presenting to the emergency department (ED) and poses a challenge to physicians given the vast differential diagnosis varying with patient age and gender. Consideration of ovarian and gynecologic pathologies is necessary in female patients to avoid missing sexually transmitted infections (STIs), pregnancy, sexual abuse, ectopic pregnancies, ovarian pathology, and more.
Evaluation of Pregnancy Outcomes Among Women With Decreased Fetal Movements
Authors: Turner Jessica M. , Flenady Vicki , Ellwood David , Coory Michael , Kumar Sailesh
Published: November 2021

(Abstracted from JAMA Network Open 2021;4(4):e215071)

Decreased fetal movement (DFM) has previously been associated with stillbirth and other adverse perinatal outcomes. Several guidelines highlight the importance of DFM as a sign associated with a risk of stillbirth; however, there is limited national guidance to incorporate this monitoring into stillbirth reduction strategies.
Effects of a Patient Experience–Based Virtual Reality Blended Learning Program on Nursing Students
Authors: Kim Hyeon-Young , Chun Jiyoung
Published: November 2021

When provided with opportunities to view the world from the patients' perspective, nursing students can experience the same practical occurrences and feelings that patients encounter, consequently becoming more aware of their discomfort and pain. This study aimed to evaluate the performance of the patient experience virtual reality blended learning program developed for nursing students. This study is significant in that it presents a program that enables nursing students to not only experience being perioperative patients themselves but also experience their conditions in places other than hospitals, which are generally used as training locations. The analytical results of this study indicated that nursing students who virtually experienced the conditions of perioperative patients through virtual reality blended learning showed increased levels of empathy, positive attitudes toward patient safety treatment, confidence in nursing care, and clinical skill performance. The developed program in this study blended various teaching methods with a virtual reality platform to help junior nursing students with practical and effective perioperative training increase their levels of empathy by simulating the experiences and perspectives of perioperative patients.
DEVELOPMENT AND VALIDATION OF AN EXPLAINABLE ARTIFICIAL INTELLIGENCE FRAMEWORK FOR MACULAR DISEASE DIAGNOSIS BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES
Authors: Lv Bin , Li Shuang , Liu Yang , Wang Wei , Li Hongyang , Zhang Xiaoyue , Sha Yanhui , Yang Xiufen , Yang Yang , Wang Yue , Zhang Chengfen , Wang Yanling , Lv Chuanfeng , Xie Guotong , Wang Kang
Published: November 2021

Purpose:

To develop and validate an artificial intelligence framework for identifying multiple retinal lesions at image level and performing an explainable macular disease diagnosis at eye level in optical coherence tomography images.

Methods:

A total of 26,815 optical coherence tomography images were collected from 865 eyes, and 9 retinal lesions and 3 macular diseases were labeled by ophthalmologists, including diabetic macular edema and dry/wet age-related macular degeneration. We applied deep learning to classify retinal lesions at image level and random forests to achieve an explainable disease diagnosis at eye level. The performance of the integrated two-stage framework was evaluated and compared with human experts.

Results:

On testing data set of 2,480 optical coherence tomography images from 80 eyes, the deep learning model achieved an average area under curve of 0.978 (95% confidence interval, 0.971–0.983) for lesion classification. In addition, random forests performed accurate disease diagnosis with a 0% error rate, which achieved the same accuracy as one of the human experts and was better than the other three experts. It also revealed that the detection of specific lesions in the center of macular region had more contribution to macular disease diagnosis.

Conclusion:

The integrated method achieved high accuracy and interpretability in retinal lesion classification and macular disease diagnosis in optical coherence tomography images and could have the potential to facilitate the clinical diagnosis.
Working Conditions and Long-Term Sickness Absence Due to Mental Disorders
Authors: Heinonen Noora , Lallukka Tea , Lahti Jouni , Pietiläinen Olli , Nordquist Hilla , Mänty Minna , Katainen Anu , Kouvonen Anne
Published: November 2021

Objective:

We examined associations between working conditions and long-term sickness absence due to mental disorders (LTSA-MD) among younger female public sector employees from different employment sectors.

Methods:

Survey data collected in 2017 (n = 3048) among 19- to 39-year-old female employees of the City of Helsinki, Finland, were used to examine job demands, job control, physical workload, computer work, and covariates. Register data on LTSA-MD were used over 1-year follow-up. Negative binomial regression models were applied.

Results:

Adverse psychosocial and physical working conditions were associated with higher LTSA-MD during the follow-up. Health and social care workers had the highest number of days of LTSA-MD.

Conclusion:

Working conditions are important factors when aiming to prevent LTSA-MD among younger employees, in the health and social care sector in particular.
Operationalizing Postdischarge Recovery From Laparoscopic Sacrocolpopexy for the Preoperative Consultative Visit
Authors: Heit Michael , Carpenter Janet S. , Chen Chen X. , Rand Kevin L.
Published: November 2021

(Abstracted from Female Pelvic Med Reconstr Surg 2021;27:427–431)

One of the most common questions from patients following surgery is: “What is my expected recovery time?” The answer serves as a benchmark to assess their progress against those undergoing similar procedures. Not addressing this expectation can result in poor patient satisfaction.
Human Immunodeficiency Virus transmission by HIV Risk Group and Along the HIV Care Continuum: A Contrast of 6 US Cities
Authors: Zang Xiao , Mah Cassandra , Quan Amanda My Linh , Min Jeong Eun , Armstrong Wendy S. , Behrends Czarina N. , Del Rio Carlos , Dombrowski Julia C. , Feaster Daniel J. , Kirk Gregory D. , Marshall Brandon D.L. , Mehta Shruti H. , Metsch Lisa R. , Pandya Ankur , Schackman Bruce R. , Shoptaw Steven , Strathdee Steffanie A. , Krebs Emanuel , Nosyk Bohdan ,   on behalf of the Localized HIV Modeling Study Group
Published: November 2021

Background:

Understanding the sources of HIV transmission provides a basis for prioritizing HIV prevention resources in specific geographic regions and populations. This study estimated the number, proportion, and rate of HIV transmissions attributable to individuals along the HIV care continuum within different HIV transmission risk groups in 6 US cities.

Methods:

We used a dynamic, compartmental HIV transmission model that draws on racial behavior–specific or ethnic behavior–specific and risk behavior–specific linkage to HIV care and use of HIV prevention services from local, state, and national surveillance sources. We estimated the rate and number of HIV transmissions attributable to individuals in the stage of acute undiagnosed HIV, nonacute undiagnosed HIV, HIV diagnosed but antiretroviral therapy (ART) naïve, off ART, and on ART, stratified by HIV transmission group for the 2019 calendar year.

Results:

Individuals with undiagnosed nonacute HIV infection accounted for the highest proportion of total transmissions in every city, ranging from 36.8% (26.7%–44.9%) in New York City to 64.9% (47.0%–71.6%) in Baltimore. Individuals who had discontinued ART contributed to the second highest percentage of total infections in 4 of 6 cities. Individuals with acute HIV had the highest transmission rate per 100 person-years, ranging from 76.4 (58.9–135.9) in Miami to 160.2 (85.7–302.8) in Baltimore.

Conclusion:

These findings underline the importance of both early diagnosis and improved ART retention for ending the HIV epidemic in the United States. Differences in the sources of transmission across cities indicate that localized priority setting to effectively address diverse microepidemics at different stages of epidemic control is necessary.
Effect of an Unsanctioned Safe Consumption Site in the United States on Syringe Sharing, Rushed Injections, and Isolated Injection Drug Use: A Longitudinal Cohort Analysis
Authors: Suen Leslie W. , Davidson Peter J. , Browne Erica N. , Lambdin Barrot H. , Wenger Lynn D. , Kral Alex H.
Published: November 2021

Background:

HIV and other medical complications of drug use, including overdose, are rising among people who inject drugs in the United States (US). Risk of complications and mortality increase with injection behaviors such as syringe sharing, rushing injections, and injecting in isolated places. Studies suggest safe consumption sites (SCS) reduce high-risk injection behaviors by offering sterile syringes and a safe, supervised space to consume drugs, although this has yet to be evaluated in the US.

Setting:

An unsanctioned SCS in an undisclosed US location.

Methods:

From 2018 to 2019, we recruited people who inject drugs using targeted sampling methods (N = 494) and conducted interviews at baseline, 6-, and 12-months. We sought to determine associations of past-month SCS use with past-month receptive syringe sharing, rushed injections, and injections in isolated places. We analyzed data using inverse probability of treatment weighted Poisson regression models. Generalized estimating equations accounted for repeated measures.

Results:

Fifty-two (11%) participants had past-month SCS use. Participants with past-month SCS use had decreased rates of receptive syringe sharing (Incident rate ratio [IRR] 0.17, 95% CI: 0.03 to 1.02) and injecting in an isolated location (IRR 0.77, 95% CI: 0.54 to 1.27) compared with those without past-month SCS use, although results were not statistically conclusive. Rate of rushed injections was only slightly lower (IRR 0.94, 95% CI: 0.70 to 1.30).

Conclusion:

SCS may show benefit in reducing high-risk injection practices, and legal sanctioning of an SCS may offer further advantages. SCS implementation should be considered to help reduce the spread of HIV, overdose mortality, and prevent other medical complications of injection drug use.
Even violins can cry: specifically vocal emotional behaviours also drive the perception of emotions in non-vocal music
Authors: Bedoya D. , Arias P. , Rachman L. , Liuni M. , Canonne C. , Goupil L. , Aucouturier J.-J.
Published: November 2021

A wealth of theoretical and empirical arguments have suggested that music triggers emotional responses by resembling the inflections of expressive vocalizations, but have done so using low-level acoustic parameters (pitch, loudness, speed) that, in fact, may not be processed by the listener in reference to human voice. Here, we take the opportunity of the recent availability of computational models that allow the simulation of three specifically vocal emotional behaviours: smiling, vocal tremor and vocal roughness. When applied to musical material, we find that these three acoustic manipulations trigger emotional perceptions that are remarkably similar to those observed on speech and scream sounds, and identical across musician and non-musician listeners. Strikingly, this not only applied to singing voice with and without musical background, but also to purely instrumental material.

This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part I)’.
Predicting strength from aggressive vocalizations versus speech in African bushland and urban communities
Authors: Kleisner Karel , Leongómez Juan David , Pisanski Katarzyna , Fiala Vojtěch , Cornec Clément , Groyecka-Bernard Agata , Butovskaya Marina , Reby David , Sorokowski Piotr , Akoko Robert Mbe
Published: November 2021

The human voice carries information about a vocalizer's physical strength that listeners can perceive and that may influence mate choice and intrasexual competition. Yet, reliable acoustic correlates of strength in human speech remain unclear. Compared to speech, aggressive nonverbal vocalizations (roars) may function to maximize perceived strength, suggesting that their acoustic structure has been selected to communicate formidability, similar to the vocal threat displays of other animals. Here, we test this prediction in two non-WEIRD African samples: an urban community of Cameroonians and rural nomadic Hadza hunter–gatherers in the Tanzanian bushlands. Participants produced standardized speech and volitional roars and provided handgrip strength measures. Using acoustic analysis and information-theoretic multi-model inference and averaging techniques, we show that strength can be measured from both speech and roars, and as predicted, strength is more reliably gauged from roars than vowels, words or greetings. The acoustic structure of roars explains 40–70% of the variance in actual strength within adults of either sex. However, strength is predicted by multiple acoustic parameters whose combinations vary by sex, sample and vocal type. Thus, while roars may maximally signal strength, more research is needed to uncover consistent and likely interacting acoustic correlates of strength in the human voice.

This article is part of the theme issue ‘Voice modulation: from origin and mechanism to social impact (Part I)’.
Biomolecule sulphation and novel methylations related to Guillain-Barré syndrome-associated Campylobacter jejuni serotype HS:19
Authors: Heikema Astrid P. , Strepis Nikolaos , Horst-Kreft Deborah , Huynh Steven , Zomer Aldert , Kelly David J. , Cooper Kerry K. , Parker Craig T.
Published: November 2021

Campylobacter jejuni

strains that produce sialylated lipooligosaccharides (LOS) can cause the immune-mediated disease Guillain-Barré syndrome (GBS). The risk of GBS after infection with

C. jejuni

Penner serotype HS:19 is estimated to be at least six times higher than the average risk. Aside from LOS biosynthesis genes, genomic characteristics that promote an increased risk for GBS following

C. jejuni

HS:19 infection, remain uncharacterized. We hypothesized that strains with the HS:19 serotype have unique genomic features that explain the increased risk for GBS. We performed genome sequencing, alignments, single nucleotide polymorphisms' analysis and methylome characterization on a subset, and pan-genome analysis on a large number of genomes to compare HS:19 with non-HS:19

C. jejuni

genome sequences. Comparison of 36

C. jejuni

HS:19 with 874

C. jejuni

non-HS:19 genome sequences led to the identification of three single genes and ten clusters containing contiguous genes that were significantly associated with

C. jejuni

HS:19. One gene cluster of seven genes, localized downstream of the capsular biosynthesis locus, was related to sulphation of biomolecules. This cluster also encoded the campylobacter sialyl transferase Cst-I. Interestingly, sulphated bacterial biomolecules such as polysaccharides can promote immune responses and, therefore, (in the presence of sialic acid) may play a role in the development of GBS. Additional gene clusters included those involved in persistence-mediated pathogenicity and gene clusters involved in restriction-modification systems. Furthermore, characterization of methylomes of two HS:19 strains exhibited novel methylation patterns (5′-CATG-3 and 5′-m6AGTNNNNNNRTTG-3) that could differentially effect gene-expression patterns of

C. jejuni

HS:19 strains. Our study provides novel insight into specific genetic features and possible virulence factors of

C. jejuni

associated with the HS:19 serotype that may explain the increased risk of GBS.
Colistin resistance in Escherichia coli confers protection of the cytoplasmic but not outer membrane from the polymyxin antibiotic
Authors: Humphrey Madeleine , Larrouy-Maumus Gerald J. , Furniss R. Christopher D. , Mavridou Despoina A. I. , Sabnis Akshay , Edwards Andrew M.
Published: November 2021

Colistin is a polymyxin antibiotic of last resort for the treatment of infections caused by multi-drug-resistant Gram-negative bacteria. By targeting lipopolysaccharide (LPS), the antibiotic disrupts both the outer and cytoplasmic membranes, leading to bacterial death and lysis. Colistin resistance in

Escherichia coli

occurs via mutations in the chromosome or the acquisition of mobilized colistin-resistance (mcr) genes. Both these colistin-resistance mechanisms result in chemical modifications to the LPS, with positively charged moieties added at the cytoplasmic membrane before the LPS is transported to the outer membrane. We have previously shown that MCR-1-mediated LPS modification protects the cytoplasmic but not the outer membrane from damage caused by colistin, enabling bacterial survival. However, it remains unclear whether this observation extends to colistin resistance conferred by other mcr genes, or resistance due to chromosomal mutations. Using a panel of clinical

E. coli

that had acquired mcr −1, –1.5, −2, –3, −3.2 or −5, or had acquired polymyxin resistance independently of mcr genes, we found that almost all isolates were susceptible to colistin-mediated permeabilization of the outer, but not cytoplasmic, membrane. Furthermore, we showed that permeabilization of the outer membrane of colistin-resistant isolates by the polymyxin is in turn sufficient to sensitize bacteria to the antibiotic rifampicin, which normally cannot cross the LPS monolayer. These findings demonstrate that colistin resistance in these

E. coli

isolates is due to protection of the cytoplasmic but not outer membrane from colistin-mediated damage, regardless of the mechanism of resistance.
Analysis of cellular and synaptic mechanisms behind spontaneous cortical activity in vitro: Insights from optimization of spiking neuronal network models
Authors: Aćimović Jugoslava , Mäki-Marttunen Tuomo , Teppola Heidi , Linne Marja-Leena
Published: November 2021

Spontaneous network bursts, the intervals of intense network-wide activity interleaved with longer periods of sparse activity, are a hallmark phenomenon observed in cortical networks at postnatal developmental stages. Generation, propagation and termination of network bursts depend on a combination of synaptic, cellular and network mechanisms; however, the interplay between these mechanisms is not fully understood. We study this interplay in silico, using a new data-driven framework for generating spiking neuronal networks fitted to the microelectrode array recordings. We recorded the network bursting activity from rat postnatal cortical networks under several pharmacological conditions. In each condition, the function of specific excitatory and inhibitory synaptic receptors was reduced in order to examine their impact on global network dynamics. The obtained data was used to develop two complementary model fitting protocols for automatic model generation. These protocols allowed us to disentangle systematically the modeled cellular and synaptic mechanisms that affect the observed network bursts. We confirmed that the change in excitatory and inhibitory synaptic transmission in silico, consistent with pharmacological conditions, can account for the changes in network bursts relative to the control data. Reproducing the exact recorded network bursts statistics required adapting both the synaptic transmission and the cellular excitability separately for each pharmacological condition. Our results bring new understanding of the complex interplay between cellular, synaptic and network mechanisms supporting the burst dynamics. While here we focused on analysis of in vitro data, our approach can be applied ex vivo and in vivo given that the appropriate experimental data is available.

New & Noteworthy

We studied the role of synaptic mechanisms in shaping the neural population activity by proposing a new method to combine experimental data and data-driven computational modeling based on spiking neuronal networks. We analyze a dataset recorded from postnatal rat cortical cultures in vitro under the pharmacological influence of excitatory and inhibitory synaptic receptor antagonists. Our computational model identifies neurobiological mechanisms necessary to reproduce the changes in population activity seen across pharmacological conditions.
Blood pressure and the kidney cortex transcriptome response to high sodium diet challenge in female nonhuman primates
Authors: Riojas Angelica M. , Spradling-Reeves Kimberly D. , Shade Robert E. , Puppala Sobha R. , Christensen Clinton L. , Birnbaum Shifra , Glenn Jeremy P. , Li Cun , Shaltout Hossam , Hall-Ursone Shannan , Cox Laura A.
Published: November 2021

Blood pressure (BP) is influenced by genetic variation and sodium intake. Ninety percent of Americans consume more than the AHA recommended amount of sodium. Studies on the impact of genetic variation and sodium intake on BP in nonhuman primates (NHP) to date have focused on males. We hypothesized that variation in renal transcriptional networks correlate with BP response to high dietary sodium in female baboons. Sodium-naïve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 betaestradiol, and ultrasound-guided kidney biopsies for RNA-Seq BP were collected at the end of each diet. BP was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP.

Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Cell type composition of renal biopsies was consistent among all animals for both diets. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. Identification of mechanisms underlying regulators that influence BP will inform better therapies towards greater precision medicine for women.
Comparative transcriptomics identifies the transcription factors BRANCHED1 and TCP4, as well as the microRNA miR166 as candidate genes involved in the evolutionary transition from dehiscent to indehiscent fruits in Lepidium (Brassicaceae)
Authors: Gramzow Lydia , Klupsch Katharina , Fernández Pozo Noé , Hölzer Martin , Marz Manja , Rensing Stefan A. , Theißen Günter
Published: November 2021

Background

Fruits are the seed-bearing structures of flowering plants and are highly diverse in terms of morphology, texture and maturation. Dehiscent fruits split open upon maturation to discharge their seeds while indehiscent fruits are dispersed as a whole. Indehiscent fruits evolved from dehiscent fruits several times independently in the crucifer family (Brassicaceae). The fruits of Lepidium appelianum, for example, are indehiscent while the fruits of the closely related L. campestre are dehiscent. Here, we investigate the molecular and genetic mechanisms underlying the evolutionary transition from dehiscent to indehiscent fruits using these two Lepidium species as model system.

Results

We have sequenced the transcriptomes and small RNAs of floral buds, flowers and fruits of L. appelianum and L. campestre and analyzed differentially expressed genes (DEGs) and differently differentially expressed genes (DDEGs). DEGs are genes that show significantly different transcript levels in the same structures (buds, flowers and fruits) in different species, or in different structures in the same species. DDEGs are genes for which the change in expression level between two structures is significantly different in one species than in the other. Comparing the two species, the highest number of DEGs was found in flowers, followed by fruits and floral buds while the highest number of DDEGs was found in fruits versus flowers followed by flowers versus floral buds. Several gene ontology terms related to cell wall synthesis and degradation were overrepresented in different sets of DEGs highlighting the importance of these processes for fruit opening. Furthermore, the fruit valve identity genes FRUITFUL and YABBY3 were among the DEGs identified. Finally, the microRNA miR166 as well as the TCP transcription factors BRANCHED1 (BRC1) and TCP FAMILY TRANSCRIPTION FACTOR 4 (TCP4) were found to be DDEGs.

Conclusions

Our study reveals differences in gene expression between dehiscent and indehiscent fruits and uncovers miR166, BRC1 and TCP4 as possible causes for the evolutionary transition from dehiscent to indehiscent fruits in Lepidium.
Anisotropic Interaction and Motion States of Locusts in a Hopper Band
Authors: Weinburd Jasper , Landsberg Jacob , Kravtsova Anna , Lam Shanni , Sharma Tarush , Simpson Stephen J , Sword Gregory A , Buhl Jerome
Published: November 2021

Swarming locusts present a quintessential example of animal collective motion. Juvenile locusts march and hop across the ground in coordinated groups called hopper bands. Composed of up to millions of insects, hopper bands exhibit aligned motion and various collective structures. These groups are well-documented in the field, but the individual insects themselves are typically studied in much smaller groups in laboratory experiments. We present the first trajectory data that detail the movement of individual locusts within a hopper band in a natural setting. Using automated video tracking, we derive our data from footage of four distinct hopper bands of the Australian plague locust,Chortoicetes terminifera. We reconstruct nearly twenty-thousand individual trajectories composed of over 3.3 million locust positions. We classify these data into three motion states: stationary, walking, and hopping. Distributions of relative neighbor positions reveal anisotropies that depend on motion state. Stationary locusts have high-density areas distributed around them apparently at random. Walking locusts have a low-density area in front of them. Hopping locusts have low-density areas in front and behind them. Our results suggest novel insect interactions, namely that locusts change their motion to avoid colliding with neighbors in front of them.