bluuebunny/crossref_metadata_2025 huggingface dataset:
Representation of frequency-modulated sweeps in the cochlear nucleus of the big brown bat
Authors: Simmons Andrea Megela , Warnecke Michaela , Simmons James A.
Published: October 2023

The cochlear nucleus (CN) receives ipsilateral input from the auditory nerve and projects to other auditory brainstem nuclei. Little is known about CN processing of signals used for echolocation. This study recorded multiple unit activity in the CN of anesthetized big brown bats (Eptesicus fuscus) to ultrasonic frequency-modulated (FM) sweeps differing in sweep direction. FM up-sweeps evoke larger peak amplitudes at shorter onset latencies and with smaller amplitude-latency trading ratios than FM down-sweeps. Variability of onset latencies is in the tens of microsecond ranges, indicating sharp temporal precision in the CN for coding of FM signals.
Are envelope stress responses essential for persistence to β-lactams in
Escherichia coli
?
Authors: Rousseau Clothilde J. , Fraikin Nathan , Zedek Safia , Van Melderen Laurence
Published: October 2023

Bacterial persistence to antibiotics defines the ability of small sub-populations of sensitive cells within an isogenic population to survive high doses of bactericidal antibiotics. Here, we investigated the importance of the five main envelope stress responses (ESRs) of
Escherichia coli
in persistence to five bactericidal β-lactam antibiotics by combining classical time-kill curve experiments and single-cell analysis using time-lapse microscopy. We showed that the survival frequency of mutants for the Bae, Cpx, Psp, and Rcs systems treated with different β-lactams is comparable to that of the wild-type strain, indicating that these ESRs do not play a direct role in persistence to β-lactams. Since the σ
E
-encoding gene is essential, we could not directly test its role. Using fluorescent reporters to monitor the activation of ESRs, we observed that σ
E
is induced by high doses of meropenem. However, the dynamics of σ
E
activation during meropenem treatment did not reveal any difference in persister cells compared to the bulk of the population, indicating that σ
E
activation is not a hallmark of persistence. The Bae, Cpx, Psp, and Rcs responses were neither induced by ampicillin nor by meropenem. However, pre-induction of the Rcs system by polymyxin B increased survival to meropenem in an Rcs-dependent manner, suggesting that this ESR might confer some yet uncharacterized advantages during meropenem treatment or at the post-antibiotic recovery step. Altogether, our data suggest that ESRs are not key actors in
E. coli
persistence to β-lactams in the conditions we tested.
Locations of membrane protein production in a cyanobacterium
Authors: Mahbub Moontaha , Mullineaux Conrad W.
Published: October 2023

Cyanobacteria show an unusually complex prokaryotic cell structure including a distinct intracytoplasmic membrane system, the thylakoid membranes that are the site of the photosynthetic light reactions. The thylakoid and plasma membranes have sharply distinct proteomes, but the mechanisms that target proteins to a specific membrane remain poorly understood. Here, we investigate the locations of translation of thylakoid and plasma membrane proteins in the model unicellular cyanobacterium
Synechococcus elongatus
PCC 7942. We use fluorescent
in situ
hybridization to probe the locations of mRNAs encoding membrane-integral proteins, plus Green Fluorescent Protein tagging of the RplL subunit to reveal the location of ribosomes under different conditions. We show that membrane-integral thylakoid and plasma membrane proteins are translated in different locations. Thylakoid membrane proteins are translated in patches at the innermost thylakoid membrane surface facing the nucleoid. However, different proteins are translated in different patches, even when they are subunits of the same multiprotein complex. This implies that translation is distributed over the proximal thylakoid surface, with newly inserted proteins migrating within the membrane prior to incorporation into complexes. mRNAs encoding plasma membrane proteins form patches at the plasma membrane. Ribosomes can be observed at similar locations near the thylakoid and plasma membranes, with more ribosomes near the plasma membrane when conditions force rapid production of plasma membrane proteins. There must be routes for ribosomes and mRNAs past the thylakoids to the plasma membrane. We infer a system to chaperone plasma membrane mRNAs to prevent their translation prior to arrival at the correct membrane.

IMPORTANCE

Cyanobacteria have a complex and distinct membrane system within the cytoplasm, the thylakoid membranes that house the photosynthetic light reactions. The thylakoid and plasma membranes contain distinct sets of proteins, but the steps that target proteins to the two membranes remain unclear. Knowledge of the protein sorting rules will be crucial for the biotechnological re-engineering of cyanobacterial cells, and for understanding the evolutionary development of the thylakoids. Here, we probe the subcellular locations of the mRNAs that encode cyanobacterial membrane proteins and the ribosomes that translate them. We show that thylakoid and plasma membrane proteins are produced at different locations, providing the first direct evidence for a sorting mechanism that operates prior to protein translation.
Corrected and republished from: “VP4 Is a Determinant of Alpha-Defensin Modulation of Rotaviral Infection”
Authors: Hu Ciara T. , Diaz Karina , Yang Linda C. , Sharma Anjali , Greenberg Harry B. , Smith Jason G.
Published: October 2023

Fecal-oral pathogens encounter constitutively expressed enteric alpha-defensins in the intestine during replication and transmission. Alpha-defensins can be potently antiviral and antibacterial; however, their primary sequences, the number of isoforms, and their activity against specific microorganisms often vary greatly between species, reflecting adaptation to species-specific pathogens. Therefore, alpha-defensins might influence not only microbial evolution and tissue tropism within a host but also species tropism and zoonotic potential. To investigate these concepts, we generated a panel of enteric and myeloid alpha-defensins from humans, rhesus macaques, and mice and tested their activity against group A rotaviruses, an important enteric viral pathogen of humans and animals. Rotaviral adaptation to the rhesus macaque correlated with resistance to rhesus enteric but not myeloid alpha-defensins and sensitivity to human alpha-defensins. Infection by mouse and human rotaviruses was either resistant to or increased by host enteric alpha-defensins, although the effects of cross-species alpha-defensins did not follow an obvious pattern. Because infection by all rotaviruses tested was resistant to or enhanced by enteric alpha-defensins from their hosts, exposure to alpha-defensins may have shaped their evolution. We then used a genetic approach to identify the viral attachment and penetration protein, VP4, as a determinant of alpha-defensin sensitivity. Our results provide a foundation for future studies of the VP4-dependent mechanism of defensin neutralization, highlight the species-specific activities of alpha-defensins, and focus future efforts on a broader range of rotaviruses that differ in VP4 to uncover the potential for enteric alpha-defensins to influence species tropism.

Importance

Rotavirus is a leading cause of severe diarrhea in young children. Like other fecal-oral pathogens, rotaviruses encounter abundant, constitutively expressed defensins in the small intestine. These peptides are a vital part of the vertebrate innate immune system. By investigating the impact that defensins from multiple species have on the infectivity of different strains of rotavirus, we show that some rotaviral infections can be inhibited by defensins. We also found that rotaviruses may have evolved resistance to defensins in the intestine of their host species, and some even appropriate defensins to increase their infectivity. Because rotaviruses infect a broad range of animals and rotaviral infections are highly prevalent in children, identifying immune defenses against infection and how they vary across species and among viral genotypes is important for our understanding of the evolution, transmission, and zoonotic potential of these viruses as well as the improvement of vaccines.
Activation of AIM2 by hepatitis B virus results in antiviral immunity that suppresses hepatitis C virus during coinfection
Authors: Li Yongqi , Yang Yang , Li Tianyang , Wang Zhengmin , Gao Chunfeng , Deng Rilin , Ma Faxiang , Li Xinyang , Ma Licong , Tian Renyun , Li Huiyi , Zhu Haizhen , Zeng Lei , Gao Yanhang , Lv Guoyue , Niu Junqi , Crispe Ian Nicholas , Tu Zhengkun
Published: October 2023

Hepatitis B virus (HBV) infection in immunocompetent adults is mostly self-limiting, whereas Hepatitis C virus (HCV) infection more often becomes chronic, suggesting that HBV is more susceptible to the host immune response. It is unclear how HBV induces effective antiviral immunity, but HBV also causes anti-HCV immunity leading to lower HCV viral loads in co-infected patients. Here, we found that a pathway in which HBV dsDNA is sensed by the inflammasome protein absent in melanoma-2, leading to caspase-1 activation in monocytes, cleavage of pro-IL-18 and secretion of IL-18 protein, activation of NK cells, and their synthesis of interferon-γ. Such activation could suppress not only HBV but also HCV replication, suggesting a mechanism through which the two viruses could engage in cross-talk during coinfection.

IMPORTANCE

Clinical data suggest that Hepatitis C virus (HCV) levels are generally lower in Hepatitis B virus (HBV) co-infected patients, but the mechanism is unknown. Here, we show that HBV, but not HCV, activated absent in melanoma-2. This in turn results in inflammasome-mediated cleavage of pro-IL-18, leading to an innate immune activation cascade that results in increased interferon-γ, suppressing both viruses.
The L-DBF vaccine cross protects mice against different
Shigella
serotypes after prior exposure to the pathogen
Authors: Lu Ti , Howlader Debaki R. , Das Sayan , Dietz Zackary K. , Nagel Aaron C. , Whittier Sean K. , Picking William D. , Picking Wendy L.
Published: October 2023

Shigellosis (bacillary dysentery) is a severe diarrheal disease caused by members of the genus
Shigella
, which results in 90 million cases annually around the world. The
Shigella
type III secretion system (T3SS) is a specialized secretion system that is the primary virulence factor it uses to infect the colonic mucosa. The type III secretion apparatus (T3SA) proteins IpaB and IpaD, as well as the genetic fusion, DBF, have been demonstrated to protect mice from
Shigella
spp. infection in a lethal pulmonary model. In a previous study, we fused LTA1, the active moiety of lethal toxin from enterotoxigenic
Escherichia coli
to DBF to produce a self-adjuvanting vaccine candidate L-DBF, which cross-protected mice against four serotypes of
Shigella flexneri
and
Shigella sonnei
. Here, we exposed mice with one or two sublethal doses of
S. flexneri
2a to identify whether the immune response induced by L-DBF in the host would be affected by prior infection by homologous or heterologous
Shigella
serotypes. We demonstrate that pre-infection with two sublethal doses of
S. flexneri
2a did not elicit cross-protection against
S. sonnei
, while vaccination with L-DBF did. Our results indicate that L-DBF is a feasible vaccine candidate that offers cross-protection against
Shigella
’s different serotypes even after prior exposure to the pathogen. This work provides a proof of concept that a novel subunit vaccine can not only protect a naïve host from
Shigella
challenge, but also can protect against challenge after prior infection by the same or different
Shigella
serotypes.

IMPORTANCE

Shigellosis is endemic to low- and middle-income regions of the world where children are especially vulnerable. In many cases, there are pre-existing antibodies in the local population and the effect of prior exposure should be considered in the development and testing of vaccines against
Shigella
infection. Our study shows that L-DBF-induced immune responses are not adversely affected by prior exposure to this pathogen. Moreover, somewhat different cytokine profiles were observed in the lungs of vaccinated mice not having been exposed to
Shigella
, suggesting that the immune responses elicited by
Shigella
infection and L-DBF vaccination follow different pathways.
Discovery of a new highly pathogenic toxin involved in insect sepsis
Authors: Zhang Yuan , Li Hao , Wang Fang , Liu Chang , Reddy Gadi V. P. , Li Hu , Li Zhihong , Sun Yucheng , Zhao Zihua
Published: October 2023

Insect sepsis is a severe consequence that arises from the invasion of the hemocoel by symbionts of entomopathogenic nematodes and bacteria. In the present study, we unveiled the heightened virulence of the entomopathogenic nematode
Steinernema feltiae
and the entomopathogenic bacteria
Xenorhabdus bovienii
, which operate symbiotically, against the wax moth
Galleria mellonella
. Maximum mortality was observed at 25°C while the optimal infestation efficiency was 20 nematodes per host. After infestation,
G. mellonella
displayed rapid darkening and softening, accompanied by an escalated esterase activity at 9 h. The
X. bovienii
, released by
S. feltiae
, underwent substantial proliferation and discharged toxins that attacked hemocytes, thus triggering extensive hemolysis and sepsis. The host
G. mellonella
was usually killed within 24 h due to disseminated septicemia. Additionally,
X. bovienii
infestation led to the upregulation of metabolites like 3-hydroxyanthranilic acid. Strikingly, we identified the perilous actinomycin D, generated through kynurenine metabolites, representing a novel biomarker of insect sepsis. Furthermore, a comprehensive transcriptomic analysis unveiled a noteworthy upregulation of gene expression associated with actinomycin D. Overall,
X. bovienii
induced apoptosis and sepsis through actinomycin D production, indicating its pivotal role in infestation activity. These findings open up new avenues for studying the mechanism of sepsis and developing innovative biotic pesticides.

IMPORTANCE

As a current biocontrol resource, entomopathogenic nematodes and their symbiotic bacterium can produce many toxin factors to trigger insect sepsis, having the potential to promote sustainable pest management. In this study, we found
Steinernema feltiae
and
Xenorhabdus bovienii
were highly virulent against the insects. After infective juvenile injection,
Galleria mellonella
quickly turned black and softened with increasing esterase activity. Simultaneously,
X. bovienii
attacked hemocytes and released toxic components, resulting in extensive hemolysis and sepsis. Then, we applied high-resolution mass spectrometry-based metabolomics and found multiple substances were upregulated in the host hemolymph. We found extremely hazardous actinomycin D produced via 3-hydroxyanthranilic acid metabolites. Moreover, a combined transcriptomic analysis revealed that gene expression of proteins associated with actinomycin D was upregulated. Our research revealed actinomycin D might be responsible for the infestation activity of
X. bovienii
, indicating a new direction for exploring the sepsis mechanism and developing novel biotic pesticides.
Phosphorus starvation response and PhoB-independent utilization of organic phosphate sources by
Salmonella enterica
Authors: Bruna Roberto E. , Kendra Christopher G. , Pontes Mauricio H.
Published: October 2023

Inorganic orthophosphate (Pi, PO
4
3−
) is the preferred phosphorus (P) source of most living cells. In enteric bacterial species such as
Salmonella enterica
serovar Typhimurium (
Salmonella
), removal of Pi from the growth medium activates a dedicated two-component signal transduction system which is composed of the membrane-bound sensor kinase PhoR and its cognate transcriptional regulator PhoB. Activated PhoB promotes transcription of genes that are involved in adaptations to low Pi conditions, such as high-affinity Pi transporters and genes required for the assimilation of alternative P sources, allowing bacteria to adapt to low Pi environments. Here, we characterize the PhoB-dependent and independent transcriptional changes elicited by
Salmonella
in response to P starvation. We identify a set of organic molecules that can serve as the sole P source and pinpoint genes that are involved in their assimilation. Intriguingly, a number of these genes are not under PhoB/PhoR control, indicating that in the absence of environmental Pi,
Salmonella
may fulfill its biosynthetic demands for P without activating a transcriptional response to Pi starvation.

IMPORTANCE

Phosphorus (P) is the fifth most abundant element in living cells. This element is acquired mainly as inorganic phosphate (Pi, PO
4
3−
). In enteric bacteria, P starvation activates a two-component signal transduction system which is composed of the membrane sensor protein PhoR and its cognate transcription regulator PhoB. PhoB, in turn, promotes the transcription of genes that help maintain Pi homeostasis. Here, we characterize the P starvation response of the bacterium
Salmonella enterica
. We determine the PhoB-dependent and independent transcriptional changes promoted by P starvation and identify proteins enabling the utilization of a range of organic substrates as sole P sources. We show that transcription and activity of a subset of these proteins are independent of PhoB and Pi availability. These results establish that
Salmonella enterica
can maintain Pi homeostasis and repress PhoB/PhoR activation even when cells are grown in medium lacking Pi.
Predation has a significant impact on the complexity and stability of microbial food webs in subalpine lakes
Authors: Guo Ping , Li Cui , Liu Jinxain , Chai Baofeng
Published: October 2023

Microbial food webs are drivers of material circulation and energy flow in lake ecosystems. The structural shifting of microbial food webs has important implications for the function of lake ecosystems. However, we continue to lack a clear understanding of the mechanisms underlying the complexity and stability of microbial food web structures. In this study, we investigated the diversity and structure of protist communities and bacterial communities by using DNA meta-barcoding to reveal the key factors affecting the complexity and stability of microbial food webs in subalpine lakes. Our analysis shows that significant seasonal variations occurred in protist taxonomic and functional communities (e.g., algivores, bacterivores, and phototrophs), which were mainly controlled by hydrological and nutrient parameters such as temperature, pH, and NH
4
+
-N. Based on the network approach, the most complex food webs in the summer exhibited the lowest stability. We also found that the trophic interaction between bacterivorous protozoans and bacteria was the main factor significantly having influence on microbial food web complexity and stability (
P
< 0.01). Moreover, biotic factors (i.e., bacterivorous protozoan composition) were better predictors of the relative abundance of several bacteria (Proteobacteria and Cyanobacteria) as prey than abiotic factors. Thus, these results suggest that predation is essential for the complexity and stability of the microbial food webs in lake ecosystems. Our findings suggest that understanding these complex interactions of microbial food webs is critical for ecosystem management and for predicting the ecological consequences of future climate changes in aquatic ecosystems.

IMPORTANCE

As an important part of microbial food webs, protists transfer organic carbon and nutrients to higher trophic levels in aquatic ecosystems. Protist predation often influences the abundance and composition of bacterial communities. However, we still do not understand whether and how predation affects the complexity and stability of microbial food webs. This study assessed the seasonal dynamic characteristics and driving factors of microbial food webs in terms of complexity and stability. Our findings have implications for future surveys to reveal the effects of climate and environmental changes.
Strength of the winter North Atlantic jet stream has deviated from its natural trend under anthropogenic warming
Authors: Li Miaofa , Cai Binggui , Marković Slobodan B. , Wang Luo , Hao Qingzhen , Baker Andy , Gavrilov Milivoj B. , Jiang Liyuan , Wang Fang , Wang Xuefeng , Wang Lisheng , Ma Zhibang , Xiao Jule , Guo Zhengtang
Published: October 2023

The North Atlantic jet stream (NAJ) has a profound impact on the climate of the North Atlantic–European sector, especially in winter. Observations show that the winter NAJ (NAJw) has strengthened over the past ~140 yr. However, it remains unclear whether this long-term trend has deviated from the natural variability. Here, we present a 2500-yr-long reconstruction of NAJw strength using high-quality stalagmite δ18O records from southeastern Europe. Our results show that the NAJw weakened during both the Roman Warm Period (300 B.C.–A.D. 200) and the Medieval Warm Period (A.D. 900–1250) but that it has strengthened under anthropogenic warming (since A.D. 1850). This indicates that its current trend has already deviated from the natural variability. The best explanation for this present anomalous trend of NAJw strength is that it was triggered by the appearance of the North Atlantic warming hole under anthropogenic forcing. This anomalous trend suggests that continued global warming may further strengthen the NAJw in the future.
Diffuse pulmonary meningotheliomatosis: a rare cause of multiple pulmonary nodules
Authors: Healy Orla , O'Callaghan Marissa , Deegan Alex , McCarthy Cormac
Published: October 2023

This case describes a woman in her 50s who presented with recurrent lower respiratory tract infections. She was an ex-smoker and had worked on a livestock farm for many years. Chest radiograph and CT of the chest revealed multiple bilateral pulmonary nodules. Bronchoalveolar lavage and transbronchial biopsy did not confirm a unifying diagnosis and thus, surgical biopsy was pursued. Video-assisted thoracoscopic surgical guided biopsy of the right upper, middle and lower lobes demonstrated intraparenchymal minute nodules, consisting of bland epithelioid cells without any evidence of malignancy. The nodules stained positive for neural cell adhesion molecule (CD56) and progesterone receptor with weakly positive epithelial membrane antigen and smooth muscle actin. The combination of this characteristic staining pattern, the diffuse subcentimetre nature of the nodules and this clinical presentation fit with a diagnosis of the ultra-rare pulmonary disease, diffuse pulmonary meningotheliomatosis (DPM). This case highlights a rare cause of bilateral diffuse pulmonary nodules and thus, the breadth of differential diagnoses that need to be considered when approaching such a finding. Careful history-taking and thorough workup is often needed, typically requiring input from multiple specialties. DPM, while rare, should not be overlooked when considering the underlying cause of this presentation, especially in female patients. This case reiterates how common clinical presentations can unveil rare conditions and the contributions of physicians, pathologists and radiologists in the diagnosis and management of these complex diseases.
Benign paroxysmal positional vertigo in a young child
Authors: Chuang Fred , Corbitt Matthew , Tjahjono Richard , Whitfield Bernard
Published: October 2023

A girl in her early childhood presented to a regional otolaryngology outpatient clinic with classic signs of benign paroxysmal positional vertigo (BPPV). She reported episodic dizziness when rolling in a supine position. She did not convey any other associated audiovestibular symptoms. A bedside Dix-Hallpike test confirmed geotropic rotational nystagmus indicative of lateral canal BPPV. Due to her young age, limited communicative abilities and concerns for more sinister underlying pathology, a complete neurological examination, MRI and pure tone audiometry were performed. After two sessions of Epley’s manoeuvre, she was symptom-free. At her 3-month follow-up, the patient denied any recurrent episodes of vertigo.
UsingAll of Usdata to examine the mental health change during COVID-19 pandemic among people living with HIV: A longitudinal study protocol
Authors: Qiao Shan , Zhang Jiajia , Liang Chen , Li Xiaoming
Published: October 2023

Introduction

The COVID-19 pandemic has negatively affected people’s mental health around the globe. Such effects may be especially compounded among some vulnerable populations such as people living with HIV (PLWH). However, large-scale data on mental health outcomes among PLWH are limited. Few studies have also identified potential protective factors for mental health outcomes.

Methods and analysis

Guided by theories of resilience and socioecology, we will leverage multiple datasets from National Institutes of Health’s Cloud-basedAll of UsProgramme including electronic health records (EHRs), a series of COVID-19 Participant Experience (COPE) Surveys conducted from May 2020 to February 2021, and other self-reported survey data to achieve two specific aims: (1) to examine the mental health outcome changes during COVID-19 pandemic among PLWH by employing both EHR data (2018–2022) and survey data (2020–2021) in theAll of UsProgramme; and (2) to identify potential protective factors based on COPE Survey data for mental health outcomes at multiple socioecological levels including individual level (eg, coping strategy), interpersonal level (eg, social support) and health institutional level (eg, health service accessibility), adjusting for pre-existing health conditions including psychiatric disorders and other relevant factors (eg, COVID-19 infection). Interaction terms will be included in the multivariable analysis to identify different socially disadvantaged or stigmatised subgroups.

Ethics and dissemination

The study has been approved by the institutional review board at the University of South Carolina (Pro00124044). Study findings will be disseminated through presentations at academic conferences and publications in peer-reviewed journals.
Effectiveness of an intervention to increase uptake of voluntary medical male circumcision among men with sexually transmitted infections in Malawi: a preinterventional and postinterventional study
Authors: Matoga Mitch M , Kudowa Evaristar , Ndalama Beatrice , Bonongwe Naomi , Mathiya Esther , Jere Edward , Kamtambe Blessings , Chagomerana Maganizo , Chasela Charles , Jewett Sara , Hosseinipour Mina C
Published: October 2023

Objective

To evaluate the effect a multistrategy demand-creation and linkage intervention on voluntary medical male circumcision (VMMC) uptake, time to VMMC and predictors of VMMC uptake among men with sexually transmitted infections (STIs).

Design

Pragmatic preinterventional and postinterventional quasi-experimental study combined with a prospective observational design.

Setting

A public and specialised STI clinic in Lilongwe, Malawi.

Population

Uncircumcised men who presented to the STI clinic.

Methods and intervention

The intervention consisted of transport reimbursement (‘R’), intensified health education (‘I’) and short-messaging services/telephonic tracing (‘Te’), abbreviated (RITe). A preintervention phase was conducted at baseline while RITe was rolled-out in the intervention phase in a sequential manner called implementation blocks: ‘I’ only—block 1; ‘I+Te’—block 2 and RITe—block 3.

Main outcome measures

Primary: VMMC uptake and time to VMMC for the full intervention and for each block. Secondary: predictors of VMMC uptake.

Results

A total of 2230 uncircumcised men presented to the STI clinic. The mean age was 29 years (SD±9), 58% were married/cohabiting, HIV prevalence was 6.4% and 43% had urethral discharge. Compared with standard of care (8/514, 1.6%), uptake increased by 100% during the intervention period (55/1716, 3.2%) (p=0.048). ‘I’ (25/731, 113%, p=0.044) and RITe (17/477, 125%, p=0.044) significantly increased VMMC uptake. The median time to VMMC was shorter during the intervention period (6 days, IQR: 0, 13) compared with standard of care (15 days, IQR: 9, 18). There was no significant incremental effect on VMMC uptake and time to VMMC between blocks. Men with genital warts were 18 times more likely to receive VMMC (adjusted relative risk=18.74, 95% CI: 2.041 to 172.453).

Conclusions

Our intervention addressing barriers to VMMC improved VMMC uptake and time to VMMC among uncircumcised men with STIs, an important subpopulation for VMMC prioritisation.

Trial registration number

NCT04677374.
Study protocol for a case series: implementation and evaluation of an integrated mental and physical healthcare programme to screen for mental health symptoms in people with epilepsy
Authors: Winsor Alice Afua , Ebelthite Candice , Onih Jemima , Nicholson Timothy R , Pal Deb K , Richardson Mark
Published: October 2023

Introduction

The prevalence of mental health symptoms in people with epilepsy (PWE) is elevated compared with that of the general population. These symptoms can negatively impact epilepsy management and patient outcomes but can be treated once recognised. It is, therefore, important to screen for these symptoms to identify needs and put in place appropriate support. Unfortunately, mental health symptoms are rarely addressed in epilepsy services due to time constraints, lack of resources and communication between psychological and medical professionals. These barriers can result in diagnostic overshadowing, where symptoms may be attributed to the disease and reduce the level of support PWE receive. Implementing an online screening tool embedded in the electronic health record (EHR) platform with supported referral pathways may remove some of these barriers.

Methods and analysis

We will follow the Integrating Mental and Physical Healthcare: Research Training and Services framework, which is a routine clinical data collection tool used by clinical teams to electronically screen psychological symptoms among patients with long-term physical health conditions. Patient outcomes including mental health, physical health and psychosocial outcomes will be collected and uploaded to the EHR platform in real-time. An appropriate referral pathway will be recommended depending on severity of the outcome scores. We will initially pilot the tool for individuals aged 13 years and above through epilepsy clinics at King’s College Hospital. Following this, the acceptability and feasibility of the tool will be assessed at baseline, 6 and 12 months.

Ethics and dissemination

Ethics approval was obtained from the National Health Service Research Ethics Committee of South Central—Oxford C, reference: 21/EM/0205. This study is expected to inform the use of integrated electronic mental health screening for youth in epilepsy clinics and improve access to psychological support. The findings will be disseminated through academic peer-reviewed journals, poster presentations and scientific meetings.
Association between spinal and non-spinal health conditions reported in epidemiological studies: a scoping review protocol
Authors: Green Bart N , Johnson Claire D , Crawford Cindy , Tavares Patricia A , Murnaghan Kent , Haldeman Scott , Hurwitz Eric L , Yang Haiou , de Luca Katie
Published: October 2023

Introduction

The increasing prevalence of coexisting health conditions poses a challenge to healthcare providers and healthcare systems. Spinal pain (eg, neck and back pain) and spinal pathologies (eg, osteoporotic fractures and degenerative spinal disease) exist concurrently with other non-spinal health conditions (NSHC). However, the scope of what associations may exist among these co-occurring conditions is unclear. Therefore, this scoping review aims to map the epidemiological literature that reports associations between spine-related pain and pathologies (SPPs) and NSHCs.

Methods and analysis

This scoping review will follow the JBI protocol and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We will systematically search the literature using key words and MeSH terms for SPPs and NSHCs. Terminology/vocabulary for NSHCs will include those for communicable and non-communicable diseases as reported by WHO Global Burden of Disease reports. Five databases will be searched from inception: MEDLINE, EMBASE, APA PsycInfo, Scopus and Web of Science Core Collection. Papers published in English, in peer-reviewed journals, including measures of association between SPPs and NSHCs and using observational epidemiologic study designs will be included. Excluded will be studies of cadaveric, animal or health behaviours; studies with no measures of association and non-observational epidemiologic studies. Results will include the number of studies, the studies that have evaluated the measures of association and the frequency of the studied associations between SPPs and NSHCs. Results will be reported in tables and diagrams. Themes of comorbidities will be synthesised into a descriptive report.

Ethics and dissemination

This scoping review was deemed exempt from ethics review. This review will provide a comprehensive overview of the literature that reports associations between SPPs and NSHCs to inform future research initiatives and practices. Results will be disseminated through publication in peer-reviewed journals and research conferences.

Registration details

https://osf.io/w49u3.
Participate CP 2: optimising participation in physically active leisure for children with cerebral palsy – protocol for a phase III randomised controlled trial
Authors: Sakzewski Leanne , Reedman Sarah Elizabeth , Elliott Catherine , Ziviani Jenny , Novak Iona , Trost Stewart , Majnemer Annette , Comans Tracy , Shikako Keiko , Ware Robert S , McNamara Lynda , Williams Sian , Keramat Syed Afroz , Brookes Denise , Boyd Roslyn N
Published: October 2023

Introduction

Children with cerebral palsy (CP) participate less in physical activities and have increased sedentary behaviour compared with typically developing peers. Participate CP is a participation-focused therapy intervention for children with CP with demonstrated efficacy in a phase II randomised controlled trial (RCT) to increase perceived performance of physical activity participation goals. This study will test the effectiveness of Participate CP in a multisite phase III RCT.

Methods and analysis

One hundred children with CP, aged 8–14 years, classified Gross Motor Function Classification System levels I–IV will be randomised to either (1) receive Participate CP once/week for 1 hour for 12 weeks, or (2) waitlist control, usual care group. The waitlist group will then receive Participate CP following the 26-week retention time point. Outcomes will be assessed at baseline, 12 weeks and then 26 weeks post baseline. The primary outcomes are (1) self-reported participation goal performance on the Canadian Occupational Performance Measure at 12 weeks and (2) daily time in moderate-to-vigorous physical activity. Secondary outcomes include home and community participation frequency, involvement and environmental supportiveness, contextual barriers to participation, quality of life, intrinsic motivation for physical activities, child perception of an autonomy-supportive climate for physical activities and physical literacy at 12 and 26 weeks post study entry.

Ethics and dissemination

The Children’s Health Queensland Hospital and Health Service, The University of Queensland and the New Zealand Health and Disability Ethics Committees have approved this study. Findings will be disseminated in peer-reviewed journals and conference presentations.

Trial registration number

ACTRN12618000206224.
Comparison of the taste and acceptability of a new high protein ice cream (Nottingham-Ice cream) with standard hospital milkshake oral nutritional supplement in older people with fragility fractures: a short report
Authors: Marsh Kirandeep , Avery Amanda , Taylor Rachael , Cameron Maribel , Sahota Opinder
Published: October 2023

Introduction

Oral nutritional supplement (ONS) prescription iscommonly recommended for older patients with hip fractures. However, ONS compliance is often low. Ice cream may be a promising nutritional intervention. Using a Plan-Do-Study Act methodology we describe the second cycle of a project using an ice cream based nutritional supplement called Nottingham-Ice cream (N-ICE CREAM) to address malnutrition in older adults. The project aimed to identify whether N-ICE CREAM is a suitable option/alternative to standard ONS.

Methods

Fifty older (≥ 65 years) inpatients with hip or spine fractures were recruited. Both groups received two days each of N-ICE CREAMand milkshake ONS. We measured compliance, acceptability (rating 0“dislike a lot” to 7 “like a lot”), attitudes towards prescription length (rating 0 “very unconfident” to 4 “very confident”) and preference.

Results

Mean (standard deviation, SD) patient age was 80.6 (7.7) years. The majority (n = 21, 67.7%) preferred N-ICE CREAM. Mean compliance to N-ICE CREAM was greater in both groups (group A (n = 22) 69.9 (30.0)% and group B (n = 26) 56.3 (39.3)%) compared to milkshake ONS (group A (n = 22) 43.4 (4.7)% and group B (n = 26) 53.6 ± (40.2)%). Mean acceptability ratings were higher for N-ICE CREAM, thus the overall impression score was greater. Confidence score for both products decreased with increasing time.

Conclusions

N-ICE CREAM is more accepted by older patients with hip or spine fractures compared to milkshake ONS. Further research should explore long-term compliance and clinical outcomes.
Cost-benefits and environmental impact of the no-biopsy approach for the diagnosis of coeliac disease in adults
Authors: Shiha Mohamed G , Nandi Nicoletta , Hutchinson Andrew J , Raju Suneil A , Tai Foong Way David , Elli Luca , Penny Hugo A , Sanders David Surendran
Published: October 2023

Objective

Recent evidence suggests that adult patients with IgA tissue transglutaminase levels of ≥10× the upper limit of normal could be accurately diagnosed with coeliac disease without undergoing endoscopy and biopsy. We aimed to evaluate the cost-benefits and the environmental impact of implementing the no-biopsy approach for diagnosing coeliac disease in clinical practice.

Design

We calculated the overall direct and indirect costs of the conventional serology-biopsy approach and the no-biopsy approach for the diagnosis of coeliac disease based on the national average unit costs and the Office of National Statistics data. We further estimated the environmental impact of avoiding endoscopy based on the estimated greenhouse gas emissions from endoscopy.

Results

Approximately 3000 endoscopies for suspected coeliac disease could be avoided each year in the UK. Implementing the no-biopsy approach for the diagnosis of coeliac disease in adults could save the National Health Service over £2.5 million in direct and indirect costs per annum and reduce endoscopy carbon footprint by 87 tonnes of CO2per year, equivalent to greenhouse gas emissions from driving 222 875 miles, carbon emissions from charging over 10 million smartphones and the carbon sequestrated by 1438 trees grown for 10 years.

Conclusion

The implementation of this non-invasive green approach could be an essential first step in the ‘Reduce’ strategy advocated by the British Society of Gastroenterology and other international endoscopy societies for sustainable endoscopy practice.
Magnetic dipole moments of bottom-charm baryons in light-cone QCD
Authors: Özdem Ulaş
Published: October 2023

The magnetic dipole moments of the doubly-heavy baryons include significant data on their inner structure and geometric shape. Moreover, understanding the electromagnetic properties of doubly-heavy baryons is the key to confinement and heavy flavor effects. Inspired by this, we extract the magnetic dipole moments of the spin-$$\frac{1}{2}$$

1
2

bottom-charm baryons utilizing the QCD light-cone sum rule with considering the distribution amplitudes of the photon. The magnetic dipole moments are obtained as $$\mu _{\Xi _{bc}^{+}} = -0.50^{+0.14}_{-0.12}~\mu _{N}$$

μ

Ξ

bc

+

=
-
0
.

50

-
0.12

+
0.14

μ
N

, $$\mu _{\Xi _{bc}^{0}} = 0.39^{+0.06}_{-0.05}~\mu _{N}$$

μ

Ξ

bc

0

=
0
.

39

-
0.05

+
0.06

μ
N

and $$\mu _{\Omega _{bc}^{0}} = 0.38^{+0.05}_{-0.04} ~\mu _{N}$$

μ

Ω

bc

0

=
0
.

38

-
0.04

+
0.05

μ
N

, $$\mu _{\Xi _{bc}^{\prime +}} = 0.57^{+0.13}_{-0.12}~\mu _{N}$$

μ

Ξ

bc

′
+

=
0
.

57

-
0.12

+
0.13

μ
N

, $$\mu _{\Xi _{bc}^{\prime 0}} =-0.29^{+0.07}_{-0.06}~\mu _{N}$$

μ

Ξ

bc

′
0

=
-
0
.

29

-
0.06

+
0.07

μ
N

and $$\mu _{\Omega _{bc}^{\prime 0}} = -0.26^{+0.06}_{-0.05}~\mu _{N}$$

μ

Ω

bc

′
0

=
-
0
.

26

-
0.05

+
0.06

μ
N

. Comparing the results obtained on the magnetic dipole moments of the $$\Omega ^{(\prime )0}_{bc}$$

Ω

bc

(
′
)
0

baryon with those of the $$\Xi ^{(\prime )0}_{bc}$$

Ξ

bc

(
′
)
0

baryon, the U-symmetry is minimally broken. We have compared our results with other theoretical predictions that could be a useful complementary tool for the interpretation of the doubly-heavy baryon sector, and we observe that they are not in mutual agreement with each other.
Schwinger poles of the three-gluon vertex: symmetry and dynamics
Authors: Aguilar A. C. , Ferreira M. N. , Oliveira B. M. , Papavassiliou J. , Santos L. R.
Published: October 2023

The implementation of the Schwinger mechanism endows gluons with a nonperturbative mass through the formation of special massless poles in the fundamental QCD vertices; due to their longitudinal character, these poles do not cause divergences in on-shell amplitudes, but induce detectable effects in the Green’s functions of the theory. Particularly important in this theoretical setup is the three-gluon vertex, whose pole content extends beyond the minimal structure required for the generation of a gluon mass. In the present work we analyze these additional pole patterns by means of two distinct, but ultimately equivalent, methods: the Slavnov–Taylor identity satisfied by the three-gluon vertex, and the nonlinear Schwinger–Dyson equation that governs the dynamical evolution of this vertex. Our analysis reveals that the Slavnov–Taylor identity imposes strict model-independent constraints on the associated residues, preventing them from vanishing. Approximate versions of these constraints are subsequently recovered from the Schwinger–Dyson equation, once the elements responsible for the activation of the Schwinger mechanism have been duly incorporated. The excellent coincidence between the two approaches exposes a profound connection between symmetry and dynamics, and serves as a nontrivial self-consistency test of this particular mass generating scenario.
The Dynamics of Jupiter's and Saturn's Weather Layers: A Synthesis After Cassini and Juno
Authors: Read Peter L.
Published: October 2023

Until recently, observations of the giant planets of our Solar System were confined to sampling relatively shallow regions of their atmospheres, leaving many uncertainties as to the dynamics of deeper layers. The Cassini and Juno missions to Saturn and Jupiter, however, have begun to address these issues, for example, by measuring their gravity and magnetic fields. The results show that the zonally coherent jets and cloud bands extend to levels where the electrical conductivity of the fluid becomes significant, whereas large-scale vortices, such as the Great Red Spot, are relatively shallow but may have deep-seated roots. The polar regions also exhibit intense cyclonic vortices that, on Jupiter, arrange themselves into remarkably regular “vortex crystals.” Numerical models seem able to capture some of this complexity, but many issues remain unresolved, suggesting a need for models that can represent both deep and shallow processes sufficiently realistic ally to compare with observations.
Control of Cell Death in Health and Disease
Authors: Kayagaki Nobuhiko , Webster Joshua D. , Newton Kim
Published: October 2023

Apoptosis, necroptosis, and pyroptosis are genetically programmed cell death mechanisms that eliminate obsolete, damaged, infected, and self-reactive cells. Apoptosis fragments cells in a manner that limits immune cell activation, whereas the lytic death programs of necroptosis and pyroptosis release proinflammatory intracellular contents. Apoptosis fine-tunes tissue architecture during mammalian development, promotes tissue homeostasis, and is crucial for averting cancer and autoimmunity. All three cell death mechanisms are deployed to thwart the spread of pathogens. Disabling regulators of cell death signaling in mice has revealed how excessive cell death can fuel acute or chronic inflammation. Here we review strategies for modulating cell death in the context of disease. For example, BCL-2 inhibitor venetoclax, an inducer of apoptosis, is approved for the treatment of certain hematologic malignancies. By contrast, inhibition of RIPK1, NLRP3, GSDMD, or NINJ1 to limit proinflammatory cell death and/or the release of large proinflammatory molecules from dying cells may benefit patients with inflammatory diseases.
The Neurobiology of Activational Aspects of Motivation: Exertion of Effort, Effort-Based Decision Making, and the Role of Dopamine
Authors: Salamone John D. , Correa Mercè
Published: October 2023

Motivational processes are complex and multifaceted, with both directional and activational aspects. Behavioral activation and exertion of effort are functions that enable organisms to overcome obstacles separating them from significant outcomes. In a complex environment, organisms make cost/benefit decisions, assessing work-related response costs and reinforcer preference. Animal studies have challenged the general idea that dopamine (DA) is best viewed as the reward transmitter and instead have illustrated the involvement of DA in activational and effort-related processes. Mesocorticolimbic DA is a key component of the effort-related motivational circuitry that includes multiple neurotransmitters and brain areas. Human studies have identified brain areas and transmitter systems involved in effort-based decision making and characterized the reduced selection of high-effort activities associated with motivational symptoms of depression and schizophrenia. Animal and human research on the neurochemistry of behavioral activation and effort-related processes makes an important conceptual contribution by illustrating the dissociable nature of distinct aspects of motivation.
Experimental Study on the Influence of Ultraviolet Laser Parameters on the Micro Machining Quality of Silicon Carbide Ceramic
Authors: Zhao Tianchen , Ruan Jiahong , Chen Hongyu , Deng Qianfa , Feng Kaiping
Published: October 2023

Silicon carbide(SiC) ceramics have great application value in microelectronics and semiconductors due to their small dielectric constant, high thermal conductivity, and small thermal expansion coefficient. However, due to its high hardness and brittleness, defects such as stress concentration, microcracks, and an excessively large heat-affected zone are prone to occur in traditional machining methods. In this paper, the ultra-thin SiC surface was micro-grooved by ultraviolet(UV) laser. The effects and rules of various machining parameters (scanning speed, repetition frequency, pulse width, defocus amount) in UV laser micro-grooves machining on the surface quality, machining depth, and cross-sectional morphology of SiC were studied. The experimental results showed that the surface roughness of SiC micro-grooves decrease with the increase of scanning speed; The relatively small surface roughness (R
a 0.72 μm) could be obtained at a scanning speed of 500 mm s−1 and a repetition frequency of 40 kHz; Under low pulse width of 5 ns, high repetition frequency of 50 kHz, and high scanning speed of 500 mm s−1, micro-grooves with a relative error of 2.3% in removal depth could be obtained; The taper of the micro-groove section first decreases and then increases with the defocus from negative to positive, and reached the minimum value of 5° when the defocus positive 0.6 mm.