bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of 18F-FES PET in Clinical Cancer Care
Authors: Huang Ya-Ting , Chen Tom Wei-Wu , Chen Li-Yu , Huang Ya-Yao , Lu Yen-Shen
Published: July 2023

Introduction

[18F]fluoroestradiol (FES) can be used for the noninvasive visualization and quantification of tumor estrogen receptor (ER) expression and activity and was FDA-approved as a diagnostic agent in May 2022 for detecting ER-positive lesions in patients with recurrent or metastatic breast cancer. PET imaging was also used to detect ER-positive lesions and malignancy among patients with uterine, ovarian, and other ER-positive solid tumors. We conducted a systemic review of the studies on FES PET imaging used among patients with cancer not limited to breast cancer to better understand the application of FES PET imaging.

Methods

PubMed/MEDLINE and Cochrane Library databases were used to perform a comprehensive and systematic search and were updated until August 15, 2022. Two authors independently reviewed the titles and abstracts of the retrieved articles by using the search algorithm and selected the articles based on the inclusion and exclusion criteria. All statistical analyses were conducted using R statistical software.

Results

Forty-three studies with 2352 patients were included in the qualitative synthesis, and 23 studies with 1388 patients were included in the quantitative analysis, which estimated the FES-positive detection rate. Thirty-two studies (77%) included breast cancer patients in 43 included studies. The FES SUVmean was higher in patients with endometrial cancer (3.4–5.3) than in those with breast cancer (2.05) and uterine sarcoma (1.1–2.6). The pooled detection rates of FES PET imaging were 0.80 for breast and 0.84 for ovarian cancer patients, both similar to that of 18F-FDG. The FES uptake threshold of 1.1 to 1.82 could detect 11.1% to 45% ER heterogeneity, but the threshold of FES uptake did not have consistent predictive ability for prognosis among patients with breast cancer, unlike uterine cancer. However, FES uptake can effectively predict and monitor treatment response, especially endocrine therapy such as estradiol, ER-blocking agents (fulvestrant and tamifoxen), and aromatase inhibitors (such as letrozole and Z-endoxifen).

Conclusions

[18F]fluoroestradiol PET is not only a convenient and accurate diagnostic imaging tool for detecting ER-expressing lesions in patients with breast and ovarian cancer but also among patients with uterine cancer. [18F]fluoroestradiol PET is a noninvasive predictive and monitoring tool for treatment response and prognosis.
68Ga–Prostate-Specific Membrane Antigen PET/CT in Imaging of Hemangiopericytoma
Authors: Kunikowska Jolanta , Chrapko Beata E.
Published: July 2023

Hemangiopericytoma is a mesenchymal neoplasm that derives from pericytes surrounding the capillaries presenting overexpression of PSMA, which can be a source of pitfall in 68Ga-PSMA-11 PET/CT. We reported 2 cases with recurrent hemangiopericytoma grade III with high expression of 68Ga-PSMA-11 in PET/CT. Based on the performed examination, one of them received targeted α-therapy with the IV injection of 225Ac-PSMA-617.
Primary Hepatocellular Carcinoma Revealed on 68Ga-DOTATATE in a Patient With Nasopharyngeal Carcinoma
Authors: Qi Mengfang , Liu Yanlin , Su Minggang , Huang Rui
Published: July 2023

A 56-year-old man underwent a prospective study (ChiCTR2300070081), which is a head-to-head comparison of 18F-FDG and 68Ga-DOTATATE PET/MR in EB-positive nonkeratinizing nasopharyngeal carcinoma after chemotherapy. Bilateral cervical abnormal lymph nodes were both detected by 18F-FDG and 68Ga-DOTATATE PET/MRI, whereas 2 hepatic lesions only were shown on 68Ga-DOTATATE, which subsequent pathologically proved to be primary hepatocellular carcinoma.
Use of 18F-PSMA PET to Distinguish Cerebral Radiation Necrosis From Tumor Recurrence
Authors: Rayamajhi Sampanna Jung , Ponisio Maria Rosana , Siegel Barry
Published: July 2023

Brain metastasis in prostate adenocarcinoma is extremely rare and usually arises in the setting of widespread osseous and visceral metastases. Surgical resection and radiation therapy, including stereotactic radiosurgery, are the mainstays of treatment for brain metastasis. Radiation necrosis is a common complication of radiotherapy for brain metastasis, and distinguishing it from tumor recurrence by MRI is difficult because of overlapping findings. We present a 73-year-old man with prostate cancer with a solitary brain metastasis where PET with 18F-piflufolostat helped detect disease recurrence in the setting of ambiguous MRI findings.
Conflict of Interest and Plastic Surgery Journal Editors
Authors: Swanson Eric
Published: July 2023

Journals insist that authors disclose their financial conflicts. However, the same standard is rarely imposed on journal editors. Surprisingly, most high-impact medical journals (about 88%) do not publish editor conflicts of interest (COIs).

The Sunshine Act makes it possible to query physician payments from industry. Importantly, some companies are exempted. The leading 5 US-based plastic surgery journals were investigated. Only chief editors and coeditors were included, for a total of 10 editors. The range of payments was US $0 to US $297,000 between 2015 and 2021. The mean payment was $90,890, or $12,984 per year. This amount may be compared with the average industry payments to all plastic surgeons, which is approximately $5000 annually.

Examples of editor COIs are considered. In one case, an article detailing important factual deficiencies in an article defending Allergan macrotextured breast implants was rejected by coeditors that included a coeditor who received payments from Allergan. An article promoting radiofrequency treatments containing previously reported data was accepted by a chief editor with a COI, who was also a coauthor.

Articles claiming improved scarring for a wound adhesive device and numerous benefits for an Allergan implant insertion funnel also found acceptance by conflicted chief editors, despite serious deficiencies.

Editor COIs should be published. Attempts to manage editor COI have not been successful. No data support a dollar limit or expiry date for COIs. Relevance and breadth of COIs are unsolved problems. The ethics of industry payments to physicians are questionable at best. An alternative option is recommended—elimination of COI for journal editors. This remedy would restore editorial integrity and avoid the need for recusals. There is precedence. About half of high-impact medical journal editors have no COIs. Industry subsidies in general should be reconsidered. Abandoning them would be in the best interest of our patients and our specialty.
Unilateral Pendular Nystagmus in Multiple Sclerosis: A Case Series
Authors: Vosoughi Amir R. , Barbosa Natalie Brossard , Micieli Jonathan , Margolin Edward
Published: July 2023

Background:

Acquired pendular nystagmus is most often seen in patients with demyelinating disease. Although it is often bilateral, rare cases may be monocular. There is paucity of data on the spectrum of clinical presentation, underlying mechanism, and response to treatment in patients with monocular pendular nystagmus.

Methods:

Retrospective case series of patients with monocular pendular nystagmus seen in 2 tertiary neuro-ophthalmology clinics between January 2019 and June 2022. All patients underwent a complete neuro-ophthalmological assessment and MRI.

Results:

We describe 5 patients (3 women) aged 31–49 with monocular pendular nystagmus. All had a diagnosis of multiple sclerosis. Three patients had horizontal and 2 had vertical pendular nystagmus. The Snellen visual acuity in the eye with pendular nystagmus varied from 20/20 to 20/200. Two patients were asymptomatic and 3 suffered visually debilitating oscillopsia. Treatment response was available for 2 patients, both of which responded well to treatment with memantine. The pendular nystagmus was observed in the eye with worse visual acuity in 4 of 5 cases (80%). Three patients had bilateral pontine lesions, and 2 had unilateral pontine lesion ipsilateral to the side of nystagmus.

Conclusions:

Monocular pendular nystagmus in adults is seen most often in patients with multiple sclerosis. Asymmetry in brainstem lesions and afferent visual input may be the culprit. Treatment with memantine may result in significant improvement in symptomatic patients.
An adiposity force induces obesity in humans independently of a normal energy balance system—a thought experiment
Authors: Sørensen Thorkild I. A.
Published: July 2023

Obesity in humans represents a cumulative retention of a tiny fraction of total energy intake as fat, which is accompanied by growth of the metabolically active, energy-demanding, lean body mass. Since the energy balance regulation operates irrespective of the excess fat storage, availability of the required energy supplies is a permissive condition for obesity development. It occurs predominantly among people genetically predisposed and/or living with social or mental challenges. I propose a theory in which the body responds to social disruptions as threats of a future lack of food by an adiposity force building a reserve of energy independent of the regulation of the energy balance. It is based on the assumption that our evolutionary development required collaboration in gathering and sharing of food, combined with precautionary measures against anticipated failing food supplies. Social challenges are perceived as such threats, which activate the adiposity force through the brain to instigate the growth of fat and lean mass by neuro-hormonal signalling. If both perceived social threats and food abundance continue, the adiposity force pushes the fat accretion process to continue without inhibition by feedback signals from the fat mass, eventually leading to more obesity, and more so among the genetically predisposed.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Reflections on the Teaching Symposium at the Microbiology Society Annual Conference 2023
Authors: Lacey Melissa M , Jones Kirsty L , Gostić Monika , Easton Victoria , Efthimiou Georgios , Kelly Bridget G , Graham Alison I
Published: July 2023

The Microbiology Society Education and Outreach Network (EON) recently hosted the Teaching Symposium at the Microbiology Society Annual Conference, sponsored by Access Microbiology. The presence of the Symposium as an established parallel session within the wider Annual Conference reflects the importance of high-quality, contemporary microbiology education and outreach delivered in an enthusiastic and inclusive manner.  At the 2023 Symposium, a variety of pedagogical research projects in higher education learning, teaching and assessment, as well as public engagement projects, were showcased through flash talks, offered talks, invited talks and posters. The event was attended by up to 70 delegates who actively engaged with all presentations. Several themes were noted throughout the day: engaging with GenZ, active learning, art in science, and engaging with non-HE audiences. Inclusivity was a key driver in the organisation of the Symposium; the room was set up to encourage discussion and participants could ask questions using an online platform as well as speaking in the room. We now encourage all speakers to consider publishing their work as a peer-reviewed article for further dissemination and impact.
The observation of taxonomic boundaries for the 16SrII and 16SrXXV phytoplasmas using genome-based delimitation
Authors: Rodrigues Jardim Bianca , Tran-Nguyen Lucy T. T. , Gambley Cherie , Al-Sadi Abdullah M. , Al-Subhi Ali M. , Foissac Xavier , Salar Pascal , Cai Hong , Yang Jun-Yi , Davis Richard , Jones Lynne , Rodoni Brendan , Constable Fiona E.
Published: July 2023

Within the 16SrII phytoplasma group, subgroups A–X have been classified based on restriction fragment length polymorphism of their 16S rRNA gene, and two species have been described, namely ‘Candidatus Phytoplasma aurantifolia’ and ‘Ca. Phytoplasma australasia’. Strains of 16SrII phytoplasmas are detected across a broad geographic range within Africa, Asia, Australia, Europe and North and South America. Historically, all members of the 16SrII group share ≥97.5 % nucleotide sequence identity of their 16S rRNA gene. In this study, we used whole genome sequences to identify the species boundaries within the 16SrII group. Whole genome analyses were done using 42 phytoplasma strains classified into seven 16SrII subgroups, five 16SrII taxa without official 16Sr subgroup classifications, and one 16SrXXV-A phytoplasma strain used as an outgroup taxon. Based on phylogenomic analyses as well as whole genome average nucleotide and average amino acid identity (ANI and AAI), eight distinct 16SrII taxa equivalent to species were identified, six of which are novel descriptions. Strains within the same species had ANI and AAI values of >97 %, and shared ≥80 % of their genomic segments based on the ANI analysis. Species also had distinct biological and/or ecological features. A 16SrII subgroup often represented a distinct species, e.g., the 16SrII-B subgroup members. Members classified within the 16SrII-A, 16SrII-D, and 16SrII-V subgroups as well as strains classified as sweet potato little leaf phytoplasmas fulfilled criteria to be included as members of a single species, but with subspecies-level relationships with each other. The 16SrXXV-A taxon was also described as a novel phytoplasma species and, based on criteria used for other bacterial families, provided evidence that it could be classified as a distinct genus from the 16SrII phytoplasmas. As more phytoplasma genome sequences become available, the classification system of these bacteria can be further refined at the genus, species, and subspecies taxonomic ranks.
Genome-based classification of the class Halobacteria and description of Haladaptataceae fam. nov. and Halorubellaceae fam. nov
Authors: Cui Can , Han Dong , Hou Jing , Cui Heng-Lin
Published: July 2023

Currently, there are four mainstream taxonomic opinions on the classification of the class

Halobacteria

at the family and order levels. The International Committee on Systematics of Prokaryotes Subcommittee on the Taxonomy of

Halobacteria

(ICSP), List of Prokaryotic names with Standing in Nomenclature (LPSN) and National Centre for Biotechnology Information (NCBI) adopted taxonomies have three to four orders and up to eight families, while the Genome Taxonomy Database (GTDB) taxonomy proposes only one order with nine families. To resolve the taxonomic inconsistency, phylogenomic analyses based on concatenated single-copy orthologous proteins and 122 concatenated conserved single-copy marker proteins were conducted to infer the taxonomic status of the current representatives of the class

Halobacteria

at the family and order levels. The current 76 genera with validly published names of the class

Halobacteria

were able to be assigned into eight families in one order. On the basis of these results, it is proposed that the current species with validly published names of the class

Halobacteria

should be remerged into the order

Halobacteriales

, then assigned to eight families, Haladaptataceae,

Haloarculaceae

,

Halobacteriaceae

,

Halococcaceae

,

Haloferacaceae

, Natronoarchaeaceae,

Natrialbaceae

and Halorubellaceae. Thus, Haladaptataceae fam. nov. is described based on

Haladaptatus

,

Halomicrococcus

and

Halorussus

and Halorubellaceae fam. nov. is proposed incorporating

Haloarchaeobius

and

Halorubellus

, respectively.
Comparative genomics reveals extensive intra-species genetic divergence of the prevalent gut commensal Ruminococcus gnavus
Authors: Abdugheni Rashidin , Liu Chang , Liu Feng-Lan , Zhou Nan , Jiang Cheng-Ying , Liu Yonghong , Li Li , Li Wen-Jun , Liu Shuang-Jiang
Published: July 2023

Ruminococcus gnavus

is prevalent in the intestines of humans and animals, and ambiguities have been reported regarding its relations with the development of diseases and host well-being. We postulate the ambiguities of its function in different cases may be attributed to strain-level variability of genomic features of

R. gnavus

. We performed comparative genomic and pathogenicity prediction analysis on 152 filtered high-quality genomes, including 4 genomes of strains isolated from healthy adults in this study. The mean G+C content of genomes of

R. gnavus

was 42.73±0.33 mol%, and the mean genome size was 3.46±0.34 Mbp. Genome-wide evolutionary analysis revealed

R. gnavus

genomes were divided into three major phylogenetic clusters. Pan–core genome analysis revealed that there was a total of 28 072 predicted genes, and the core genes, soft-core genes, shell genes and cloud genes accounted for 3.74 % (1051/28 072), 1.75 % (491/28 072), 9.88 % (2774/28 072) and 84.63 % (23 756/28 072) of the total genes, respectively. The small proportion of core genes reflected the wide divergence among

R. gnavus

strains. We found certain coding sequences with determined health benefits (such as vitamin production and arsenic detoxification), whilst some had an implication of health adversity (such as sulfide dehydrogenase subunits). The functions of the majority of core genes were unknown. The most widespread genes functioning in antibiotic resistance and virulence are tetO (tetracycline-resistance gene, present in 75 strains) and cps4J (capsular polysaccharide biosynthesis protein Cps4J encoding gene, detected in 3 genomes), respectively. Our results revealed genomic divergence and the existence of certain safety-relevant factors of

R. gnavus

. This study provides new insights for understanding the genomic features and health relevance of

R. gnavus

, and raises concerns regarding predicted prevalent pathogenicity and antibiotic resistance among most of the strains.
Killing in the name of: T6SS structure and effector diversity
Authors: Allsopp Luke P. , Bernal Patricia
Published: July 2023

The life of bacteria is challenging, to endure bacteria employ a range of mechanisms to optimize their environment, including deploying the type VI secretion system (T6SS). Acting as a bacterial crossbow, this system delivers effectors responsible for subverting host cells, killing competitors and facilitating general secretion to access common goods. Due to its importance, this lethal machine has been evolutionarily maintained, disseminated and specialized to fulfil these vital functions. In fact, T6SS structural clusters are present in over 25 % of Gram-negative bacteria, varying in number from one to six different genetic clusters per organism. Since its discovery in 2006, research on the T6SS has rapidly progressed, yielding remarkable breakthroughs. The identification and characterization of novel components of the T6SS, combined with biochemical and structural studies, have revealed fascinating mechanisms governing its assembly, loading, firing and disassembly processes. Recent findings have also demonstrated the efficacy of this system against fungal and Gram-positive cells, expanding its scope. Ongoing research continues to uncover an extensive and expanding repertoire of T6SS effectors, the genuine mediators of T6SS function. These studies are shedding light on new aspects of the biology of prokaryotic and eukaryotic organisms. This review provides a comprehensive overview of the T6SS, highlighting recent discoveries of its structure and the diversity of its effectors. Additionally, it injects a personal perspective on avenues for future research, aiming to deepen our understanding of this combative system.
Atheroma plaque microenvironment stimulates kynurenine production by macrophages to induce endothelial adhesion molecules in the context of atherogenesis
Authors: Van Dongen Kevin , Leleu Damien , Pilot Thomas , Jalil Antoine , Mangin Léa , Ménégaut Louise , Geissler Audrey , Ivanov Stoyan , Laubriet Aline , Crespy Valentin , Nguyen Maxime , Steinmetz Eric , Masson David , Thomas Charles , Gautier Thomas
Published: July 2023

Cardiovascular diseases, including atherosclerosis, are major causes of morbidity and mortality worldwide. Here, we investigate the role of the kynurenine pathway (KP) in macrophages in the context of atheroma plaque microenvironment and its impact on atherogenesis. Using an in vitro model of primary human macrophages, we observed that exposure to plaque homogenates induces a marked increase in the early steps of the KP which impacts on kynurenine production. This was confirmed by immunostaining on human plaque of carotid arteries. Further investigation into the underlying molecular mechanisms revealed that LXR signaling contributes to this plaque microenvironment-induced KP activation. We showed that kynurenine released from macrophages affected endothelial cells, leading to increased expression of ICAM-1 and VCAM-1 in an AhR-dependent manner. Consistently with the proatherogenic effects, in a cohort of atherosclerotic patients, we observed higher levels of plasma kynurenine in patients with lower extremity arterial disease. In line with the results of in vitro investigations, the plasma kynurenine levels were associated plaque oxysterol content. Using a multiple logistic regression model, we showed that plasma kynurenine was independently associated with lower extremity arterial disease in atherosclerotic patients. Altogether, our data indicate that the activation of KP in macrophages in the context of atheroma plaque is partially mediated by LXR axis and leads to the release of kynurenine. This, in turn, contributes to the exacerbation of both local and peripheral atherosclerosis particularly through the activation of endothelial cells.
Antiemetic effect of pregabalin in breast reconstruction surgery in patients after bariatric surgery: Prospective, randomized, double-blind study
Authors: Fernandes Rafael Reis , Salgado-Filho Marcello Fonseca , Graziosi Guilherme Bracco , da Silva André Luiz Viana Nery , Távora Flávio Augusto Amaral Fernandes , de Azevedo Caio Pontes , da Silva Alice Ramos Oliveira , Verçosa Nubia , Cavalcanti Ismar Lima
Published: July 2023

Introduction

Postoperative nausea and vomiting (PONV) is a common complication after general anesthesia. Pregabalin may reduce its incidence. The objective of this study was to evaluate the adjuvant antiemetic effect of pregabalin in the first 24 hours after surgery in patients undergoing breast reconstruction after bariatric surgery.

Materials and Methods

This prospective, randomized, double-blind study had 52 female patients aged between 18 and 64 years with physical status 1-2 of the American Society of Anesthesiologists who underwent breast reconstruction after bariatric surgery. The patients were divided into two groups. Patients in the control group received placebo, and those in the pregabalin group received 75 mg of pregabalin 2 hours before surgery and 75 mg 12 hours later. All patients received 4 mg dexamethasone and 4 mg ondansetron. The incidence of PONV was evaluated in the immediate postoperative period and 6 hours, 12 hours, and 24 hours later. The need for rescue doses of antiemetics and adverse events in the first 24 hours were recorded.

Results

The groups were homogeneous in clinical and treatment variables. There was no significant difference in the incidence of PONV over time in the control group (P = 0.71/no occurrence) or in the pregabalin group (P = 0.11/P = 0.26). There was no significant difference in the need for rescue antiemetic dose (P = 0.40) or in the incidence of adverse events (P = 0.51) between groups.

Conclusion

The administration of pregabalin in the first 24 hours after surgery did not significantly reduce PONV in patients undergoing breast reconstruction after bariatric surgery.
The Political Division toward COVID-19, Vaccines, Contact Tracing Apps, and A Future Pandemic Scenario in the United States: A Survey Result from A National Representative Sample
Authors: Hao Haijing , Smith Garrett , Chen Yunan , Mondal Mainack , Loh Po-Shen , Smith Staci , Page Xinru
Published: July 2023

Objectives

To investigate the attitudes and behaviors of Americans concerning the COVID-19 pandemic, COVID-19 vaccines, COVID-19 tracing apps, and the actions they believe the government should take during a public health crisis, we designed and conducted a survey during the ongoing COVID-19 emergency.

Methods

In January 2022, we administered an online survey on Prolific Academic to 302 participants in the United States, a nationally demographic representative sample. To explore differences in attitudes and opinions among demographic subgroups, we employed several statistical tests, including Mann Whitney U tests, Kruskal-Wallis tests, and chi-squared tests.

Results

Our survey results suggest that Americans’ opinions towards the COVID-19 pandemic are severely divided by their political views. There is strong partisan polarization in almost every COVID-19 related question in our survey.

Policy Implications

Our findings suggest that policy makers need to consider partisan polarization and the enormous impact it can have on people’s attitudes and behaviors during public health emergencies such as the COVID-19 pandemic. Public health experts need to consider how to convey scientific knowledge about a pandemic without allowing political views to dominate medical conversation.
NEURAL RESPONSE TO THREAT AND REWARD AMONG YOUNG ADULTS AT RISK FOR ALCOHOL USE DISORDER
Authors: Kirk-Provencher Katelyn T. , Hakimi Rosa H. , Andereas Keinada , Penner Anne E. , Gowin Joshua L.
Published: July 2023

Alcohol use disorder is 50% heritable; those with positive family histories represent an at-risk group within which we can test anticipation of threat and reward prior to development of harmful alcohol use. We examined neural correlates of the interaction between family history, threat anticipation (unpredictable threat), and monetary reward anticipation, in a sample of healthy young adults with (n=31) and without (n=44) family histories of harmful alcohol use. We used a modified Monetary Incentive Delay task with sustained threat of hearing a scream during fMRI. We examined the interaction between family history group, anticipation of threat, and anticipation of reward in the insula, nucleus accumbens, and medial prefrontal cortex. Family history positive individuals showed less activation in the left insula during both safe and threat blocks compared to family history negative individuals (p=0.005), but the groups did not differ as a function of unpredictable threat (p>0.70). We found an interaction (p=0.048) between cue and group in the right nucleus accumbens where the family history positive group showed less differentiation to the anticipation of gaining $5 and losing $5 relative to gaining $0. The family history positive group also reported less excitement for trials to gain $5 relative to gaining $0 (p<0.001). Prior to chronic heavy alcohol use, individuals with, relative to without, enriched risk may have diminished reward processing via both neural and behavioral markers to potential rewarding and negative consequences. Neural response to unpredictable threat may not be a contributing factor to risk at this stage.
Prevalence and Factors Associated with Illicit Drug and High-Risk Alcohol Use among Adolescents Living in Urban Slums of Kampala, Uganda
Authors: Kalungi Hellen , Kamacooko Onesmus , Lunkuse Jane Frances , Namutebi Joy , Naluwooza Rose , Price Matt A. , Ruzagira Eugene , Mayanja Yunia
Published: July 2023

Background

Illicit drug and high risk alcohol use among adolescents leads to poor health outcomes. We enrolled adolescents from urban slums in Kampala, Uganda, to assess baseline prevalence, and factors associated with illicit drug and high-risk alcohol consumption.

Methods

We conducted a cross-sectional study using data collected in a cohort that enrolled 14-19-year-old male and female participants from 25-March-2019 to 30-March 2020. Data was collected on social-demographics, sexual behavior and reproductive health using interviewer administered questionnaires. The main outcomes were illicit drug use and high-risk alcohol use. Data on alcohol use was collected using the Alcohol Use Disorder Identification Test (AUDIT); results were dichotomized. Factors associated with each outcome were analyzed using multivariable logistic regression.

Results

We enrolled 490 participants (60.6% female) with median age 18 (IQR 17-18) years, 91.0% had less than secondary education, 48.4% had their sexual debut before 15years, 47.1% reported paid sex in the past 3 months and 24.7% had a sexually transmitted infection (chlamydia, gonorrhea and/ or active syphilis) at enrolment.

The prevalence of illicit drug use was 34.9% while 16.1% were screened as high-risk alcohol users. Illicit drug use was associated with being male (aOR 9.62; 95% CI 5.74-16.11), being married (aOR 2.24; 95%CI 1.07-4.68) and having ≥10 paying sexual partners in the past 3 months (aOR 3.13; 95%CI 1.40-6.98). High risk alcohol use was associated with reporting sex work as the main job (aOR 3.19; 95%CI 1.02-9.94) and having experienced physical (aOR 1.96 95%CI 1.01-3.81) or emotional violence (aOR 2.08; 95%CI 1.14-3.82) from sexual partners.

Conclusion

Illicit drug and high-risk alcohol use are prevalent among adolescents involved in high risk sexual behavior and living in urban slums of Kampala. Comprehensive interventions that target substance use among this group of young people are needed and should include measures against intimate partner violence.
Temporal trends and factors associated with emergency department visits and hospitalizations in angina with no obstructive coronary artery disease (ANOCA)
Authors: Patel Shubh , Fung Marinda , Butalia Sonia , Anderson Todd J
Published: July 2023

Introduction

Angina with no obstructive coronary artery disease (ANOCA) presents diagnostic and treatment challenges, significantly burdening healthcare resources as reported in previous studies. This study assessed temporal changes in emergency department (ED) visits and hospitalizations for ANOCA and factors associated with these outcomes.

Methods/Results

We assessed a retrospective cohort of 85,573 individuals (26% with ANOCA, 31% female, mean age 62.1±12.0 years) who underwent their first cardiac catheterization for chest pain in Alberta from 2002 to 2017. Temporal trend analysis showed ED visits ranged from 26.3% to 30.7% (β=0.21 [95%CI:-0.28 to 0.70];p=0.33) for ANOCA and from 47.7% to 53.1% (β=-0.15[95%CI:-0.87 to 0.57];p=0.63) for obstructive CAD, with no temporal changes in either. Hospitalizations decreased from 6.5% to 3.8% (β=-0.28 [95%CI:-0.47 to -0.09];p=0.010) for ANOCA and from 24.8% to 15.3% (β=-1.45 [95%CI:-1.77 to -1.12];p<0.001) for obstructive CAD. Multivariable logistic regression analysis factors associated with ED visits in individuals with ANOCA included cerebrovascular disease (CEVD) (OR=1.73 [95%CI:1.40–2.15]), congestive heart failure (CHF) (OR=1.91 [95%CI:1.49–2.44]), peripheral artery disease (PAD) (OR=1.61 [95%CI:1.18–2.19), and unstable angina (UA) (versus (vs) stable angina (SA): OR=1.65 [95%CI:1.51–1.80]). Factors associated with hospitalizations in ANOCA included CEVD (OR=1.39 [95%CI:1.11–1.73]), CHF (OR=2.06 [95%CI:1.66–2.56]), hypertension (OR: 1.26 [95%CI:1.14–1.40]), PAD (OR=1.89 [95%CI:1.43–2.50]), and myocardial infarction (vs SA: OR=1.27 [95%CI:1.12–1.44]), and UA (vs SA: OR=1.36 [95%CI:1.22–1.52]).

Conclusions

ED visits for ANOCA remained stable, while hospitalizations declined over time. Understanding factors associated with recurrent visits may aid clinicians in treatment strategies.

Clinical Perspective

What is new?

This study was the first to characterize emergency department (ED) visits and assess temporal trends of ED visits and hospitalizations in individuals with ANOCA.

ED visits for individuals with ANOCA or obstructive CAD have remained stable over time, with a significant decline in hospitalizations for both groups.

In contrast to previous studies, individuals with obstructive CAD had higher ED visits and hospitalizations rates than those with ANOCA.

What are the clinical implications?

Increased recognition of ANOCA may be responsible for decreasing hospitalizations.

Despite increased awareness, individuals with ANOCA still frequently visit the ED, highlighting the need for improved education on persistent chest pain and unnecessary ED visits.

The development of specialized chest pain clinics using a multidisciplinary approach could reduce unnecessary ED visits and hospitalizations, thereby improving the quality of life for individuals with ANOCA.
Efficacy of N-163 beta-glucan in beneficially improving biomarkers of relevance to muscle function in patients with muscular dystrophies in a pilot clinical study
Authors: Raghavan Kadalraja , Sivakumar Thanasekar , Ichiyama Koji , Yamamoto Naoki , Balamurugan Mangaleswaran , Dedeepiya Vidyasagar Devaprasad , Senthilkumar Rajappa , Preethy Senthilkumar , Abraham Samuel JK
Published: July 2023

Background:

Muscular dystrophies other than Duchenne muscular dystrophy (DMD) are genetic diseases characterized by increasing muscle weakness, loss of ambulation, and ultimately cardiac and respiratory failure. There are currently no effective therapeutics available. Having demonstrated the efficacy of a N-163 strain of Aureobasidium Pullulans (Neu-REFIX) produced B-1, 3-1,6-Glucan in pre-clinical and clinical studies of Duchenne muscular dystrophy (DMD) earlier, we assessed the effectiveness of this novel Beta glucan in the other muscular dystrophies in the present study.

Methods:

In this 60-day study, six patients with muscular dystrophies other than DMD consumed one 8g gel of Neu-REFIX beta-glucan along with their usual standard of care treatment regimen, and their biomarkers of relevance to muscle function such as serum calcium (SC), creatinine phosphokinase (CPK), and alkaline phosphatase (ALP) levels along with functional improvement criteria, viz., Medical research council (MRC) scale and North Star Ambulatory assessment (NSAA) were assessed at baseline and following the intervention.

Results:

After the intervention, the SC levels significantly decreased from a mean baseline value of 9.28 mg/dL to 8.31 mg/dL (p-value = 0.02). With a p-value of 0.29, the mean CPK value dropped from 2192.33 IU/L to 1567.5 IU/L. Following the intervention, the ALP levels dropped from 200.33 to 75.5 U/L (p-value =0.15). MRC scale improved in three out of six patients. NSAA remained stable. There were no adverse effects.

Conclusion:

This study has proven the safety of Neu REFIX beta-glucan food supplement and its efficacy in improving both plasma biomarkers and functional parameters of muscle in a short duration of 2 months. Further validation by evaluation of muscle function for a longer duration is recommended to confirm the efficacy of Neu-REFIX food supplement as a potential adjuvant DMT in muscular dystrophies.
Trade-offs in a reef-building coral after six years of thermal acclimation
Authors: Roik Anna , Wall Marlene , Dobelmann Melina , Nietzer Samuel , Brefeld David , Fiesinger Anna , Reverter Miriam , Schupp Peter J. , Jackson Matthew , Rutsch Marie , Strahl Julia
Published: July 2023

Evidence is growing that reef-building corals have the capacity to acclimate to new and challenging thermal conditions by increasing their thermal resistance. This raises hopes for their future persistence in a warming world. However, potential trade-offs that accompany such resistance gains, have remained largely unexplored. We provide the first report on the physiological trade-offs in a globally abundant and ecologically relevant coral species (Pocillopora acuta), after a long-term exposure to an elevated temperature of 31 °C in comparison to conspecifics cultivated under a cooler ‘control’ thermal regime. At both temperatures, corals consistently appeared to be visually healthy throughout a six-year period. At 31 °C, corals had increased metabolic rates (both respiration and photosynthesis) that resulted in higher biomass accumulation and total energy reserves compared to the corals from the ambient regime. Further, the composition of coral host tissues shifted in favor of lipid build-up, suggesting an altered mechanism of energy storage. The increase in biomass growth came at the cost of declining skeletal growth rates and the formation of higher density skeletons. In the long-term, this trade-off will result in lower extension rates that can entail major ramifications for future reef building processes and reef community composition. Moreover, symbionts at 31 °C were physiologically more compromised with overall lower energy reserves, possibly indicating a stronger exploitation by the host and potentially a lower stress resilience. Our study provides first insights into a successful thermal acclimation mechanism that involved the prioritization of energy storage over skeletal growth, entailing higher demands on the symbionts. Our observation in this 6-year study does not align with observations of short-term studies, where elevated temperatures caused a depletion of tissue lipids in corals, which highlights the importance of studying acclimation of organisms over their relevant biological scales. Further investigations into trade-offs at biologically relevant scales and how they unfold under an acute heat stress will help to provide a more comprehensive picture of the future coral reef trajectory. Importantly, these insights will also help improve interventions aimed at increasing the thermal resilience of corals which anticipate to use thermal preconditioning treatments for stress-hardening.

Graphical abstract
Early life adversity reduces affiliative behavior towards a distressed cagemate and leads to sex-specific alterations in corticosterone responses
Authors: Breton Jocelyn M. , Cort Zoey , Demaestri Camila , Critz Madalyn , Nevins Samuel , Downend Kendall , Ofray Dayshalis , Romeo Russell D. , Bath Kevin G.
Published: July 2023

Experiencing early life adversity (ELA) alters stress physiology and increases the risk for developing psychiatric disorders. The social environment can influence dynamics of stress responding and buffer and/or transfer stress across individuals. Yet, the impact of ELA on sensitivity to the stress of others and social behavior following stress is unknown. Here, to test the impact of ELA on social and physiological responses to stress, circulating blood corticosterone (CORT) and social behaviors were assessed in adult male and female mice reared under limited bedding and nesting (LBN) or control conditions. To induce stress, one cagemate of a pair-housed cage underwent a footshock paradigm and was then returned to their unshocked partner. CORT was measured in both mice 20 or 90 minutes after stress exposure, and social behaviors were recorded and analyzed. ELA rearing influenced the CORT response to stress in a sex-specific manner. In males, both control and ELA-reared mice exhibited similar stress transfer to unshocked cagemates and similar CORT dynamics. In contrast, ELA females showed a heightened stress transfer to unshocked cagemates, and sustained elevation of CORT relative to controls, indicating enhanced stress contagion and a failure to terminate the stress response. Behaviorally, ELA females displayed decreased allogrooming and increased investigative behaviors, while ELA males showed reduced huddling. Together, these findings demonstrate that ELA influenced HPA axis dynamics, social stress contagion and social behavior. Further research is needed to unravel the underlying mechanisms and long-term consequences of ELA on stress systems and their impact on behavioral outcomes.
The influence of gene flow on population viability in an isolated urban caracal population
Authors: Kyriazis Christopher C. , Serieys Laurel E.K. , Bishop Jacqueline M. , Drouilly Marine , Viljoen Storme , Wayne Robert K. , Lohmueller Kirk E.
Published: July 2023

Wildlife populations are becoming increasingly fragmented by anthropogenic development. Such small and isolated populations often face an elevated risk of extinction, in part due to inbreeding depression. Here, we examine the genomic consequences of urbanization in a caracal (Caracal caracal) population that has become isolated in the Cape Peninsula region of the city of Cape Town, South Africa and is thought to number ∼50 individuals. We document low levels of migration into the population over the past ∼75 years, with an estimated rate of 1.3 effective migrants per generation. As a consequence of this isolation and small population size, levels of inbreeding are elevated in the contemporary Cape Peninsula population (mean FROH>1Mb=0.20). Inbreeding primarily manifests as long runs of homozygosity >10Mb, consistent with the effects of isolation due to the rapid recent growth of Cape Town. To explore how reduced migration and elevated inbreeding may impact future population dynamics, we parameterized an eco-evolutionary simulation model. We find that if migration rates do not change in the future, the population is expected to decline only slightly, with a low projected risk of extinction. However, if migration rates decline or anthropogenic mortality rates increase, the potential risk of extinction is greatly elevated. To avert a population decline, we suggest that translocating migrants into the Cape Peninsula to initiate a genetic rescue may be warranted in the near future. Our analysis highlights the utility of genomic datasets coupled with computational simulation models for investigating the influence of gene flow on population viability.
The T cell receptor sequence influences the likelihood of T cell memory formation
Authors: Lagattuta Kaitlyn A. , Nathan Aparna , Rumker Laurie , Birnbaum Michael E. , Raychaudhuri Soumya
Published: July 2023

T cell differentiation depends on activation through the T cell receptor (TCR), whose amino acid sequence varies cell to cell. Particular TCR amino acid sequences nearly guarantee Mucosal-Associated Invariant T (MAIT) and Natural Killer T (NKT) cell fates. To comprehensively define how TCR amino acids affects all T cell fates, we analyze the paired αβTCR sequence and transcriptome of 819,772 single cells. We find that hydrophobic CDR3 residues promote regulatory T cell transcriptional states in both the CD8 and CD4 lineages. Most strikingly, we find a set of TCR sequence features, concentrated in CDR2α, that promotes positive selection in the thymus as well as transition from naïve to memory in the periphery. Even among T cells that recognize the same antigen, these TCR sequence features help to explain which T cells form immunological memory, which is essential for effective pathogen response.
Simple and rewireable biomolecular building blocks for DNA machine-learning algorithms
Authors: Lee Ryan C. , Corsano Ariel , Tseng Chung Yi , Chou Leo Y. T.
Published: July 2023

Deep learning algorithms, such as neural networks, enable the processing of complex datasets with many related variables, and have applications in disease diagnosis, cell profiling, and drug discovery. Beyond its use in electronic computers, neural networks have been implemented using programmable biomolecules such as DNA. This confers unique advantages such as greater portability, ability to operate without electricity, and direct analysis of patterns of biomolecules in solution. Analogous to past bottlenecks in electronic computers, the computing power of DNA-based neural networks is limited by the ability to add more computing units, i.e. neurons. This limitation exists because current architectures require many nucleic acids to model a single neuron. Each addition of a neuron to the network compounds existing problems such as long assembly times, high background signal, and cross-talk between components. Here we test three strategies to solve this limitation and improve the scalability of DNA-based neural networks: (i) enzymatic synthesis to generate high-purity neurons, (ii) spatial patterning of neuron clusters based on their network position, and (iii) encoding neuron connectivity on a universal single-stranded DNA backbone. We show that neurons implemented via these strategies activate quickly, with high signal-to-background ratio, and respond to varying input concentrations and weights. Using this neuron design, we implemented basic neural network motifs such as cascading, fan-in, and fan-out circuits. Since this design is modular, easy to synthesize, and compatible with multiple neural network architectures, we envision it will help scale DNA-based neural networks in a variety of settings. This will enable portable computing power for applications such as portable diagnostics, compact data storage, and autonomous decision making for lab-on-a-chips.
Liquid channels withinB. subtilisbiofilms allow the escape of trapped clones and population rescue
Authors: Krishnan Nikhil , Knight Joseph , Mookherjee Abhirup , Ruiz Pestana Luis , Fusco Diana
Published: July 2023

Bacterial communities undergoing spatial expansions, such as colonies and biofilms, typically exhibit a severe loss of genetic diversity due to gene surfing, a phenomenon by which only cells close to the expanding edge have a chance of contributing to the next generation. As a result, mutants that emerge behind the front will remain trapped in the bulk of the population, even if they carry a significant growth advantage. While these findings are applicable to smooth, uniformly dense colonies, where cell spatial re-arrangement is limited, it is unclear whether they hold in bacterial communities that display complex three-dimensional morphologies, such as wrinkly biofilms.

We employ an experimental procedure that enables a rapid switch of the chemical environment with minimal physical manipulation of the cell community to investigate the fate of trapped clones carrying a selective advantage in wrinklyB. subtilisbiofilms. We find that these clones are able to use the channels underneath the wrinkles to traverse long distances and take over the expansion front. Moreover, we find that active motility is required to accomplish this task. Collectively, our findings reveal an intriguing novel role of wrinkles, as they enable potentially advantageous mutants to propel themselves towards the leading edge of the expansion and rescue the population upon environmental changes. Our results also point at motility, which has traditionally received little attention in bacterial communities growing on hard substrates, as a key mechanism for population rescue in biofilms that display complex morphologies.
Odor source distance is predictable from a time-history of odor statistics for large scale outdoor plumes
Authors: Nag Arunava , van Breugel Floris
Published: July 2023

Odor plumes in turbulent environments are intermittent and sparse. Lab-scaled experiments suggest that information about the source distance may be encoded in odor signal statistics, yet it is unclear whether useful and continuous distance estimates can be made under real-world flow conditions. Here we analyze odor signals from outdoor experiments with a sensor moving across large spatial scales in desert and forest environments to show that odor signal statistics can yield useful estimates of distance. We show that achieving accurate estimates of distance requires integrating statistics from 5-10 seconds, with a high temporal encoding of the olfactory signal of at least 20 Hz. By combining distance estimates from a linear model with wind-relative motion dynamics, we achieved source distance estimates in a 60×60 m2search area with median errors of 3-8 meters, a distance at which point odor sources are often within visual range for animals such as mosquitoes.