bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of procedural modalities in the treatment of notalgia paresthetica
Authors: Nilforoushzadeh Mohammad Ali , Ghane Yekta , Heidari Nazila , Azizi Hanieh , Fathabadi Fatemeh , Najar Nobari Niloufar , Heidari Amirhossein
Published: May 2024

Background

Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP.

Aims

We sought to comprehensively evaluate the role of procedural treatments for NP.

Methods

We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included.

Results

Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non‐pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first‐line choice or an alternative in refractory cases.

Conclusion

Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.
State attachment and gubernatorial approval
Authors: Winburn Jonathan , Fudge Daniel J. , Murphy Joseph , Griffin Bailey
Published: May 2024

Objective

The purpose of this article is to examine what drives individual attitudes toward their governor with a focus on the role of place attachment as a means of diffuse support.

Methods

Using original surveys from March and May 2020, we test the role of place attachment in explaining gubernatorial approval.

Results

We find state or place attachment is a strong predictor of gubernatorial approval especially among individuals who live in a state with a governor from the other party.

Conclusion

State attachment can be an important and unique influence on political attitudes toward state politics.
Identification of the novel HLA‐DQB1*06:466 allele by next‐generation sequencing in a Chinese cord blood donor
Authors: Zhao Shuoxian , Wang Fang , Chen Chen , Zhang Wei , Zhu Faming
Published: May 2024

HLA‐DQB1*06:466 differs from HLA‐DQB1*06:01:01:01 by a single nucleotide substitution at position 571G→A.
High CD34‐positive cell dose in matched unrelated donor allogeneic hematopoietic stem cell transplant is not associated with graft‐versus‐host disease or mortality
Authors: Avigan Zachary M. , Dias Ajoy L. , Dodge Laura E. , Arnason Jon E. , Joyce Robin M. , Liegel Jessica , Rosenblatt Jacalyn , Weinstock Matthew J. , Avigan David E. , Haspel Richard L.
Published: May 2024

Background

CD34+ stem cells serve as the primary graft source for allogeneic transplants, with a minimum of 2–4 × 106 cells/kg needed for engraftment. There are conflicting data on outcomes at high stem cell doses, with studies limited by few patients receiving doses far above the minimum target.

Study design and Methods

In this retrospective, single‐center study of patients with hematologic malignancies who underwent matched unrelated donor transplants, we assessed outcomes for engraftment, survival, relapse, and graft‐versus‐host disease (GVHD) for the highest CD34+ dose quintile (>13 × 106 cells/kg, n = 36) compared to the remaining patients (n = 139). Similar analysis was performed correlating T cell dose and outcomes.

Results

There was no difference between the groups in neutrophil engraftment, with a trend toward faster platelet engraftment. There was no significant difference in mortality (adjusted risk ratio [aRR] = 1.02, 95% confidence interval [CI] = 0.85–1.22), relapse (aRR = 1.10, 95% CI = 0.85–1.42), or overall survival by Kaplan–Meier analysis (p = .44). High CD34+ dose was not associated with higher incidence of acute GVHD (aRR = 0.99 grades II–IV, aRR = 1.18 grades III–IV) or chronic GVHD (aRR = 0.87 overall, RR = 1.21 severe). There was limited correlation between CD34+ and T cell dose (R2 = .073), and there was no significant difference in survival, relapse, or GVHD in the highest T cell dose quintile (n = 33) compared to the remaining quintiles (n = 132).

Discussion

We found no difference in survival, relapse, or GVHD incidence or severity in patients receiving CD34+ doses above prior cutoffs reported in the literature. These data do not support the routine use of graft CD34+ dose reduction.
Bilateral pyogranulomatous otitis externa with putative cartilage destruction in a dog: A severe case of auricular chondritis?
Authors: De Lucia Michela , Mendes Carolina , Bertolini Giovanna
Published: May 2024

Auricular chondritis of unknown cause was suspected in a 10‐year‐old male Bolognese dog with a five‐month history of painful bilateral nodular and ulcerative pyogranulomatous dermatitis of the pinnae with putative auricular cartilage destruction. Pain and lesions resolved with immunosuppressive doses of prednisolone, yet the condition resulted in deformity of both pinnae and external canals.
Philippine English variation in police blotters
Authors: Servano Ersweetcel C.
Published: May 2024

Philippine English variation in lexicon is visible in the language of police blotters. In the process of police blotter writing, only the English written document is used as the basis of investigation, as an attachment to court documents and as a news source. To determine the Philippine English variation in the lexicon in the English transcriptions of Cebuano oral complaints, Y. Kachru and Nelson's perspective on creativity and innovation is used to analyse the police blotters. The Philippine English variation that appears in such blotters shows how Philippine English is not a monolithic construct, but is affected by the sociolinguistic realities of the Philippines.
Wild rabbits are Leishmania infantum reservoirs in southeastern Spain
Authors: Martín‐Sánchez Joaquina , Díaz‐Sáez Victoriano , Morillas‐Márquez Francisco , Corpas‐López Victoriano , Ibáñez‐De Haro Patricia , Torres‐Llamas Andrés , Morales‐Yuste Manuel
Published: May 2024

Objective

We contribute to the understanding of the transmission dynamics of Leishmania infantum suggesting the involvement of rabbits as wild reservoirs.

Results

The prevalence of infection was 86.0% (270/314 wild rabbits) ranging from 18.2% to 100% in natural geographical regions. The estimated average parasite load was 324.8 [CI 95% 95.3–554.3] parasites per mg of ear lobe ranging from 0 to 91,597 parasites/mg per tissue section.

Conclusions

A positive correlation was found between skin parasite load in wild rabbits and human incidence with evidence of the presence of the same L. infantum genotypes in rabbits and humans, providing new epidemiological and biological basis for the consideration of wild rabbits as a relevant L. infantum wild reservoir. Molecular parasite surveillance reflects the great genotypic variability of the parasite population in wild rabbits. Most of these genotypes have also been found to infect humans, dogs and sandflies in the region. Our findings also highlight that direct genotyping of the parasite in host tissues should be used for molecular surveillance of the parasite instead of cultured isolates.
Computing Galois cohomology of a real linear algebraic group
Authors: Borovoi Mikhail , de Graaf Willem A.
Published: May 2024

Let be a linear algebraic group, not necessarily connected or reductive, over the field of real numbers . We describe a method, implemented on computer, to find the first Galois cohomology set . The output is a list of 1‐cocycles in . Moreover, we describe an implemented algorithm that, given a 1‐cocycle , finds the cocycle in the computed list to which is equivalent, together with an element of realizing the equivalence.
On Donkin's tilting module conjecture II: counterexamples
Authors: Bendel Christopher P. , Nakano Daniel K. , Pillen Cornelius , Sobaje Paul
Published: May 2024

In this paper we produce infinite families of counterexamples to Jantzen's question posed in 1980 on the existence of Weyl $p$-filtrations for Weyl modules for an algebraic group and Donkin's tilting module conjecture formulated in 1990. New techniques to exhibit explicit examples are provided along with methods to produce counterexamples in large rank from counterexamples in small rank. Counterexamples can be produced via our methods for all groups other than when the root system is of type ${\rm A}_{n}$ or ${\rm B}_{2}$.
Effects of the motor cortical theta‐burst transcranial‐focused ultrasound stimulation on the contralateral motor cortex
Authors: Xia Xue , Wang Zhen , Zeng Ke , Nankoo Jean‐François , Darmani Ghazaleh , Tran Stephanie , Ding Mandy Yi Rong , Chen Robert
Published: May 2024

Theta‐burst transcranial ultrasound stimulation (tbTUS) increases primary motor cortex (M1) excitability for at least 30 min. However, the remote effects of focal M1 tbTUS on the excitability of other cortical areas are unknown. Here, we examined the effects of left M1 tbTUS on right M1 excitability. An 80 s train of active or sham tbTUS was delivered to the left M1 in 20 healthy subjects. Before and after the tbTUS, we measured: (1) corticospinal excitability using motor‐evoked potential (MEP) amplitudes from single‐pulse transcranial magnetic stimulation (TMS) of left and right M1; (2) interhemispheric inhibition (IHI) from left to right M1 and from right to left M1 using a dual‐site paired‐pulse TMS paradigm; and (3) intracortical circuits of the right M1 with short‐interval intracortical inhibition and intracortical facilitation (ICF) using paired‐pulse TMS. Left M1 tbTUS decreased right M1 excitability as shown by decreased MEP amplitudes, increased right M1 ICF and decreased short‐interval IHI from left to right hemisphere at interstimulus interval (ISI) of 10 ms but not long‐interval IHI at interstimulus interval of 40 ms. The study showed that left M1 tbTUS can change the excitability of remote cortical areas with decreased right M1 excitability and interhemispheric inhibition. The remote effects of tbTUS should be considered when it is used in neuroscience research and as a potential neuromodulation treatment for brain disorders.

image

Key points

Transcranial ultrasound stimulation (TUS) is a novel non‐invasive brain stimulation technique for neuromodulation with the advantages of being able to achieve high spatial resolution and target deep brain structures.

A repetitive TUS protocol, with an 80 s train of theta burst patterned TUS (tbTUS), has been shown to increase primary motor cortex (M1) excitability, as well as increase alpha and beta movement‐related spectral power in distinct brain regions.

In this study, we examined on the effects of the motor cortical tbTUS on the excitability of contralateral M1 measured with MEPs elicited by transcranial magnetic stimulation.

We showed that left M1 tbTUS decreased right M1 excitability and left‐to‐right M1 interhemispheric inhibition, and increased intracortical facilitation of right M1.

These results lead to better understand the effects of tbTUS and can help the development of tbTUS for the treatment of neurological and psychiatric disorders and in neuroscience research.
Momentum-exchange interactions in a Bragg atom interferometer suppress Doppler dephasing
Authors: Luo Chengyi , Zhang Haoqing , Koh Vanessa P. W. , Wilson John D. , Chu Anjun , Holland Murray J. , Rey Ana Maria , Thompson James K.
Published: May 2024

Large ensembles of laser-cooled atoms interacting through infinite-range photon-mediated interactions are powerful platforms for quantum simulation and sensing. Here we realize momentum-exchange interactions in which pairs of atoms exchange their momentum states by collective emission and absorption of photons from a common cavity mode, a process equivalent to a spin-exchange or XX collective Heisenberg interaction. The momentum-exchange interaction leads to an observed all-to-all Ising-like interaction in a matter-wave interferometer. A many-body energy gap also emerges, effectively binding interferometer matter-wave packets together to suppress Doppler dephasing in analogy to Mössbauer spectroscopy. The tunable momentum-exchange interaction expands the capabilities of quantum interaction–enhanced matter-wave interferometry and may enable the realization of exotic behaviors, including simulations of superconductors and dynamical gauge fields.
Induction of social contagion for diverse outcomes in structured experiments in isolated villages
Authors: Airoldi Edoardo M. , Christakis Nicholas A.
Published: May 2024

Certain people occupy topological positions within social networks that enhance their effectiveness at inducing spillovers. We mapped face-to-face networks among 24,702 people in 176 isolated villages in Honduras and randomly assigned villages to targeting methods, varying the fraction of households receiving a 22-month health education package and the method by which households were chosen (randomly versus using the friendship-nomination algorithm). We assessed 117 diverse knowledge, attitude, and practice outcomes. Friendship-nomination targeting reduced the number of households needed to attain specified levels of village-wide uptake. Knowledge spread more readily than behavior, and spillovers extended to two degrees of separation. Outcomes that were intrinsically easier to adopt also manifested greater spillovers. Network targeting using friendship nomination effectively promotes population-wide improvements in welfare through social contagion.
N-type semiconducting hydrogel
Authors: Li Peiyun , Sun Wenxi , Li Jiulong , Chen Ju-Peng , Wang Xinyue , Mei Zi , Jin Guanyu , Lei Yuqiu , Xin Ruiyun , Yang Mo , Xu Jingcao , Pan Xiran , Song Cheng , Deng Xin-Yu , Lei Xun , Liu Kai , Wang Xiu , Zheng Yuting , Zhu Jia , Lv Shixian , Zhang Zhi , Dai Xiaochuan , Lei Ting
Published: May 2024

Hydrogels are an attractive category of biointerfacing materials with adjustable mechanical properties, diverse biochemical functions, and good ionic conductivity. Despite these advantages, their application in electronics has been restricted because of their lack of semiconducting properties, and they have traditionally only served as insulators or conductors. We developed single- and multiple-network hydrogels based on a water-soluble n-type semiconducting polymer, endowing conventional hydrogels with semiconducting capabilities. These hydrogels show good electron mobilities and high on/off ratios, enabling the fabrication of complementary logic circuits and signal amplifiers with low power consumption and high gains. We demonstrate that hydrogel electronics with good bioadhesive and biocompatible interface can sense and amplify electrophysiological signals with enhanced signal-to-noise ratios.
A blueprint for tumor-infiltrating B cells across human cancers
Authors: Ma Jiaqiang , Wu Yingcheng , Ma Lifeng , Yang Xupeng , Zhang Tiancheng , Song Guohe , Li Teng , Gao Ke , Shen Xia , Lin Jian , Chen Yamin , Liu Xiaoshan , Fu Yuting , Gu Xixi , Chen Zechuan , Jiang Shan , Rao Dongning , Pan Jiaomeng , Zhang Shu , Zhou Jian , Huang Chen , Shi Si , Fan Jia , Guo Guoji , Zhang Xiaoming , Gao Qiang
Published: May 2024

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell–receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell–driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell–targeting immunotherapy.
Brain-muscle communication prevents muscle aging by maintaining daily physiology
Authors: Kumar Arun , Vaca-Dempere Mireia , Mortimer Thomas , Deryagin Oleg , Smith Jacob G. , Petrus Paul , Koronowski Kevin B. , Greco Carolina M. , Segalés Jessica , Andrés Eva , Lukesova Vera , Zinna Valentina M. , Welz Patrick-Simon , Serrano Antonio L. , Perdiguero Eusebio , Sassone-Corsi Paolo , Benitah Salvador Aznar , Muñoz-Cánoves Pura
Published: May 2024

A molecular clock network is crucial for daily physiology and maintaining organismal health. We examined the interactions and importance of intratissue clock networks in muscle tissue maintenance. In arrhythmic mice showing premature aging, we created a basic clock module involving a central and a peripheral (muscle) clock. Reconstituting the brain-muscle clock network is sufficient to preserve fundamental daily homeostatic functions and prevent premature muscle aging. However, achieving whole muscle physiology requires contributions from other peripheral clocks. Mechanistically, the muscle peripheral clock acts as a gatekeeper, selectively suppressing detrimental signals from the central clock while integrating important muscle homeostatic functions. Our research reveals the interplay between the central and peripheral clocks in daily muscle function and underscores the impact of eating patterns on these interactions.
An active, stable cubic molybdenum carbide catalyst for the high-temperature reverse water-gas shift reaction
Authors: Ahmadi Khoshooei Milad , Wang Xijun , Vitale Gerardo , Formalik Filip , Kirlikovali Kent O. , Snurr Randall Q. , Pereira-Almao Pedro , Farha Omar K.
Published: May 2024

Although technologically promising, the reduction of carbon dioxide (CO
2
) to produce carbon monoxide (CO) remains economically challenging owing to the lack of an inexpensive, active, highly selective, and stable catalyst. We show that nanocrystalline cubic molybdenum carbide (α-Mo
2
C), prepared through a facile and scalable route, offers 100% selectivity for CO
2
reduction to CO while maintaining its initial equilibrium conversion at high space velocity after more than 500 hours of exposure to harsh reaction conditions at 600°C. The combination of operando and postreaction characterization of the catalyst revealed that its high activity, selectivity, and stability are attributable to crystallographic phase purity, weak CO-Mo
2
C interactions, and interstitial oxygen atoms, respectively. Mechanistic studies and density functional theory (DFT) calculations provided evidence that the reaction proceeds through an H
2
-aided redox mechanism.
Pandemics and their accelerants
The Human Disease: How We Create Pandemics, from Our Bodies to Our Beliefs
Sabrina Sholts
MIT Press, 2024. 352 pp.
Authors: Lynteris Christos
Published: May 2024

A well-researched account of the factors that drive pandemics misses an opportunity to indict broader social systems
Climate modelers grapple with their own emissions
Authors: Voosen Paul
Published: May 2024

In next round of international modeling, centers will track their carbon footprint and curb excess computing
Ancient crystals suggest early Earth had land and freshwater
Authors: Cutts Elise
Published: May 2024

Hardy zircon minerals found in Australian rocks hint that conditions for life existed 4 billion years ago
Multidrug resistance in
Salmonella
isolates of swine origin: mobile genetic elements and plasmids associated with cephalosporin resistance with potential transmission to humans
Authors: Garrido V. , Arrieta-Gisasola A. , Migura-García L. , Laorden L. , Grilló M. J.
Published: May 2024

The emergence of foodborne
Salmonella
strains carrying antimicrobial resistance (AMR) in mobile genetic elements (MGE) is a significant public health threat in a One Health context requiring continuous surveillance. Resistance to ciprofloxacin and cephalosporins is of particular concern. Since pigs are a relevant source of foodborne
Salmonella
for human beings, we studied transmissible AMR genes and MGE in a collection of 83 strains showing 9 different serovars and 15 patterns of multidrug resistant (MDR) previously isolated from pigs raised in the conventional breeding system of Northern Spain. All isolates were susceptible to ciprofloxacin and three isolates carried
bla
CMY-2
or
bla
CTX-M-9
genes responsible for cefotaxime resistance. Filter mating experiments showed that the two plasmids carrying
bla
CTX-M-9
were conjugative while that carrying
bla
CMY-2
was self-transmissible by transformation. Whole-genome sequencing and comparative analyses were performed on the isolates and plasmids. The IncC plasmid pSB109, carrying
bla
CMY-2
, was similar to one found in
S
. Reading from cattle, indicating potential horizontal transfer between serovars and animal sources. The IncHI2 plasmids pSH102 in
S
. Heidelberg and pSTM45 in
S
. Typhimurium ST34, carrying
bla
CTX-M-9
, shared similar backbones and two novel “complex class 1 integrons” containing different AMR and heavy metal genes. Our findings emphasize the importance of sequencing techniques to identify emerging AMR regions in conjugative and stable plasmids from livestock production. The presence of MGE carrying clinically relevant AMR genes raises public health concerns, requiring monitoring to mitigate the emergence of bacteria carrying AMR genes and subsequent spread through animals and food.

IMPORTANCE

The emergence of foodborne
Salmonella
strains carrying antimicrobial resistance (AMR) in mobile genetic elements (MGE) is a significant public health threat in a One Health context. Since pigs are a relevant source of foodborne
Salmonella
for humans, in this study, we investigate different aspects of AMR in a collection of 83
Salmonella
showing nine different serovars and 15 patterns of multidrug resistant (MDR) isolated from pigs raised in the conventional breeding system. Our findings emphasize the importance of sequencing techniques to identify emerging AMR regions in conjugative and stable plasmids from livestock production. The presence of MGE carrying clinically relevant AMR genes raises public health concerns, requiring monitoring to mitigate the emergence of bacteria carrying AMR genes and subsequent spread through animals and food.
Lighting the way: how the
Vibrio fischeri
model microbe reveals the complexity of Earth’s “simplest” life forms
Authors: Septer Alecia N. , Visick Karen L.
Published: May 2024

Vibrio
(
Aliivibrio
)
fischeri
’s initial rise to fame derived from its alluring production of blue-green light. Subsequent studies to probe the mechanisms underlying this bioluminescence helped the field discover the phenomenon now known as quorum sensing. Orthologs of quorum-sensing regulators (i.e., LuxR and LuxI) originally identified in
V. fischeri
were subsequently uncovered in a plethora of bacterial species, and analogous pathways were found in yet others. Over the past three decades, the study of this microbe has greatly expanded to probe the unique role of
V. fischeri
as the exclusive symbiont of the light organ of the Hawaiian bobtail squid,
Euprymna scolopes
. Buoyed by this optically amenable host and by persistent and insightful researchers who have applied novel and cross-disciplinary approaches,
V. fischeri
has developed into a robust model for microbe-host associations. It has contributed to our understanding of how bacteria experience and respond to specific, often fluxing environmental conditions and the mechanisms by which bacteria impact the development of their host. It has also deepened our understanding of numerous microbial processes such as motility and chemotaxis, biofilm formation and dispersal, and bacterial competition, and of the relevance of specific bacterial genes in the context of colonizing an animal host. Parallels in these processes between this symbiont and bacteria studied as pathogens are readily apparent, demonstrating functional conservation across diverse associations and permitting a reinterpretation of “pathogenesis.” Collectively, these advances built a foundation for microbiome studies and have positioned
V. fischeri
to continue to expand the frontiers of our understanding of the microbial world inside animals.
Whole-genome sequence of a marine bacterial strain, FRT2, belonging to the genus
Leeuwenhoekiella
, isolated from the seawater of the Obama Bay in Fukui, Japan
Authors: Machii Yuka , Tsukamoto Mao , Kataoka Takafumi , Kondo Ryuji
Published: May 2024

A marine bacterial strain, FRT2, was isolated from the surface water of the Obama Bay in Fukui, Japan. Its complete genome comprises one circular chromosome (3,806,097 bp), harboring 3,269 predicted protein- and 44-tRNA-encoding genes and 3 rRNA operons.
Spectrum of activity and mechanisms of azole–bisphosphonate synergy in pathogenic
Candida
Authors: Kane Aidan , Dinh Hue , Campbell Leona , Cain Amy K. , Hibbs David , Carter Dee
Published: May 2024

Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality. The most common
Candida
species implicated in human disease is
Candida albicans
, but other species like
Candida glabrata
are emerging. The use of azole antifungals for treatment is limited by increasing rates of resistance. This study explores repositioning bisphosphonates, which are traditionally used for osteoporosis, as antifungal synergists that can improve and revitalize the use of azoles. Risedronate, alendronate, and zoledronate (ZOL) were tested against isolates from six different species of
Candida
, and ZOL produced moderate antifungal activity and strong synergy with azoles like fluconazole (FLC), particularly in
C. glabrata
. FLC:ZOL combinations had increased fungicidal and antibiofilm activity compared to either drug alone, and the combination prevented the development of antifungal resistance. Mechanistic investigations demonstrated that the synergy was mediated by the depletion of squalene, resulting in the inhibition of ergosterol biosynthesis and a compromised membrane structure. In
C. glabrata
, synergy compromised the function of membrane-bound multidrug transporters and caused an accumulation of reactive oxygen species, which may account for its acute sensitivity to FLC:ZOL. The efficacy of FLC:ZOL
in vivo
was confirmed in a
Galleria mellonella
infection model, where combinations improved the survival of larvae infected with
C. albicans
and
C. glabrata
to a greater extent than monotherapy with FLC or ZOL, and at reduced dosages. These findings demonstrate that bisphosphonates and azoles are a promising new combination therapy for the treatment of topical candidiasis.

IMPORTANCE

Candida
is a common and often very serious opportunistic fungal pathogen. Invasive candidiasis is a prevalent cause of nosocomial infections with a high mortality rate, and mucocutaneous infections significantly impact the quality of life of millions of patients a year. These infections pose substantial clinical challenges, particularly as the currently available antifungal treatment options are limited in efficacy and often toxic. Azoles are a mainstay of antifungal therapy and work by targeting the biosynthesis of ergosterol. However, there are rising rates of acquired azole resistance in various
Candida
species, and some species are considered intrinsically resistant to most azoles. Our research demonstrates the promising therapeutic potential of synergistically enhancing azoles with non-toxic, FDA-approved bisphosphonates. Repurposing bisphosphonates as antifungal synergists can bypass much of the drug development pipeline and accelerate the translation of azole–bisphosphonate combination therapy.
Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study
Authors: Sewell Elizabeth , Cohen Susan , Zaniletti Isabella , Couture Dan , Dereddy Narendra , Coghill Carl H , Flanders Tracy M , Foy Andrew , Heuer Gregory G , Jano Eni , Kemble Nicole , Lee Stephanie , Ling Con Yee , Malaeb Shadi , Mietzsch Ulrike , Ocal Eylem , Padula Michael A , Welch Cherrie D , White Bernadette , Wilson Diane , Flibotte John
Published: May 2024

Objective

To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH).

Design

Cohort study of the Children’s Hospitals Neonatal Database from 2010 to 2022.

Setting

41 referral neonatal intensive care units (NICUs) in North America.

Patients

Infants born before 32 weeks’ gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage.

Interventions

(1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS).

Main outcome measures

Mortality and meningitis.

Results

Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort.

Conclusions

There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.
Terminal ileitis: a rare gastrointestinal manifestation of IgA vasculitis in a child
Authors: Sandhu Kirn , Mcdonald Kirsteen , Langmead Louise , Deb Protima
Published: May 2024

A girl in middle childhood was referred to the paediatric surgical team with acute colicky abdominal pain and bile-stained vomiting. This was preceded by a viral illness. Investigations revealed raised inflammatory markers, and imaging of the abdomen demonstrated ileal and jejunal thickening. Concerns were raised regarding whether she had inflammatory bowel disease. Endoscopy revealed gastritis and duodenitis, and colonoscopy was unremarkable. Video capsule endoscopy demonstrated ulcers in the jejunum and ileum.

On day 8 of admission, she developed a symmetrical purpuric rash over both ankles leading to the diagnosis of Henoch-Schonlein-related ileitis. Multidisciplinary team working led to appropriate management of the patient and avoided surgery. Video capsule endoscopy enabled visualisation of the small bowel. She was managed with 5 days of methylprednisolone followed by oral steroids. She made a good recovery with no sequelae. This case highlighted that terminal ileitis is a rare complication of IgA vasculitis with a good prognosis.
Tumour-induced osteomalacia: the long road to diagnosis and recovery
Authors: Vollmer Shobitha , Olsson Karin
Published: May 2024

Tumour-induced osteomalacia is caused by tumorous production of fibroblast growth factor 23 (FGF23) leading to urinary phosphate wasting, hypophosphataemia and decreased vitamin D activation. The resulting osteomalacia presents with muscle weakness and bone pain but progresses to multiple pathological fractures. Patients often remain undiagnosed for years with severe physical, psychological and economic ramifications. A young woman presented with multiple spontaneous fractures including bilateral femoral fractures. Laboratory tests revealed severe hypophosphataemia, elevated bone turnover markers and low to normal calcium and 25-hydroxy-vitamin D levels. Treatment with phosphate, alfalcalcidol, calcium and magnesium was initiated.68Gallium-DOTATOC positron emission tomography imaging revealed a mass in the right foot and venous sampling of FGF23 from all extremities confirmed this tumour as the culprit. Biopsy and histology were consistent with a phosphaturic mesenchymal tumour, which was surgically resected. Phosphate levels quickly normalised postoperatively but a long convalescence with hungry bone syndrome, fracture healing and physical therapy followed.
Predicting the cognitive impairment with multimodal ophthalmic imaging and artificial neural network for community screening
Authors: Jin Zi , Chen Xuhui , Jiang Chunxia , Feng Ximeng , Zou Da , Lu Yanye , Li Jinying , Ren Qiushi , Zhou Chuanqing
Published: May 2024

Background/aims

To investigate the comprehensive prediction ability for cognitive impairment in a general elder population using the combination of the multimodal ophthalmic imaging and artificial neural networks.

Methods

Patients with cognitive impairment and cognitively healthy individuals were recruited. All subjects underwent medical history, blood pressure measurement, the Montreal Cognitive Assessment, medical optometry, intraocular pressure and custom-built multimodal ophthalmic imaging, which integrated pupillary light reaction, multispectral imaging, laser speckle contrast imaging and retinal oximetry. Multidimensional parameters were analysed by Student’s t-test. Logistic regression analysis and back-propagation neural network (BPNN) were used to identify the predictive capability for cognitive impairment.

Results

This study included 104 cognitive impairment patients (61.5% female; mean (SD) age, 68.3 (9.4) years), and 94 cognitively healthy age-matched and sex-matched subjects (56.4% female; mean (SD) age, 65.9 (7.6) years). The variation of most parameters including decreased pupil constriction amplitude (CA), relative CA, average constriction velocity, venous diameter, venous blood flow and increased centred retinal reflectance in 548 nm (RC548) in cognitive impairment was consistent with previous studies while the reduced flow acceleration index and oxygen metabolism were reported for the first time. Compared with the logistic regression model, BPNN had better predictive performance (accuracy: 0.91 vs 0.69; sensitivity: 93.3% vs 61.70%; specificity: 90.0% vs 68.66%).

Conclusions

This study demonstrates retinal spectral signature alteration, neurodegeneration and angiopathy occur concurrently in cognitive impairment. The combination of multimodal ophthalmic imaging and BPNN can be a useful tool for predicting cognitive impairment with high performance for community screening.
Creating realistic anterior segment optical coherence tomography images using generative adversarial networks
Authors: Assaf Jad F , Abou Mrad Anthony , Reinstein Dan Z , Amescua Guillermo , Zakka Cyril , Archer Timothy J , Yammine Jeffrey , Lamah Elsa , Haykal Michèle , Awwad Shady T
Published: May 2024

Aims

To develop a generative adversarial network (GAN) capable of generating realistic high-resolution anterior segment optical coherence tomography (AS-OCT) images.

Methods

This study included 142 628 AS-OCT B-scans from the American University of Beirut Medical Center. The Style and WAvelet based GAN architecture was trained to generate realistic AS-OCT images and was evaluated through the Fréchet Inception Distance (FID) Score and a blinded assessment by three refractive surgeons who were asked to distinguish between real and generated images. To assess the suitability of the generated images for machine learning tasks, a convolutional neural network (CNN) was trained using a dataset of real and generated images over a classification task. The generated AS-OCT images were then upsampled using an enhanced super-resolution GAN (ESRGAN) to achieve high resolution.

Results

The generated images exhibited visual and quantitative similarity to real AS-OCT images. Quantitative similarity assessed using FID scored an average of 6.32. Surgeons scored 51.7% in identifying real versus generated images which was not significantly better than chance (p value >0.3). The CNN accuracy improved from 78% to 100% when synthetic images were added to the dataset. The ESRGAN upsampled images were objectively more realistic and accurate compared with traditional upsampling techniques by scoring a lower Learned Perceptual Image Patch Similarity of 0.0905 compared with 0.4244 of bicubic interpolation.

Conclusions

This study successfully developed and leveraged GANs capable of generating high-definition synthetic AS-OCT images that are realistic and suitable for machine learning and image analysis tasks.
Improving healthcare accessibility for pregnant women and children in the context of health system strengthening initiatives and terrorist attacks in Central Mali: a controlled interrupted time series analysis
Authors: Zombré David , Diarra Dansiné , Touré Laurence , Bonnet Emmanuel , Ridde Valery
Published: May 2024

Introduction

The Health and Social Development Program of the Mopti Region (PADSS2) project, launched in Mali’s Mopti region, targeted Universal Health Coverage (UHC). The project addressed demand-side barriers by offering an additional subsidy to household contributions, complementing existing State support (component 1). Component 2 focused on supply-side improvements, enhancing quality and coverage. Component 3 strengthened central and decentralised capacity for planning, supervision and UHC reflection, integrating gender mainstreaming. The study assessed the impact of the project on maternal and child healthcare use and explored how rising terrorist activities might affect these health outcomes.

Methods

The impact of the intervention on assisted births, prenatal care and curative consultations for children under 5 was analysed from January 2016 to December 2021. This was done using an interrupted time series analysis, incorporating a comparison group and spline regression.

Results

C1 increased assisted deliveries by 0.39% (95% CI 0.20 to 0.58] and C2 by 1.52% (95% CI 1.36 to 1.68). C1-enhanced first and fourth antenatal visits by 1.37% (95% CI 1.28 to 1.47) and 2.07% (95% CI 1.86 to 2.28), respectively, while C2 decreased them by 0.53% and 1.16% (95% CI −1.34 to −0.99). For child visits under 5, C1 and C2 showed increases of 0.32% (95% CI 0.20 to 0.43) and 1.36% (95% CI 1.27 to 1.46), respectively. In areas with terrorist attacks, child visits decreased significantly by 24.69% to 39.86% compared with unexposed areas.

Conclusion

The intervention had a limited impact on maternal and child health, falling short of expectations for a health system initiative. Understanding the varied effects of terrorism on healthcare is key to devising strategies that protect the most vulnerable in the system.
Daughter circumcision and maternal life satisfaction: a cultural moderation effect revealed across two multicountry studies
Authors: Strand Paul S , Maxwell Providence D , Trang Justin
Published: May 2024

Introduction

The present paper assessed the relationship between maternal life satisfaction (MLS) and the intergenerational transmission of female genital cutting (FGC, female circumcision). It was hypothesised that the association would be more strongly positive in countries in which FGC is more prevalent (ie, culturally normative), suggesting a practice that is socially reinforcing within sociocultural contexts in which it is common.

Methods

Across two studies with more than 85 000 participants in 15 African and Asian countries, mothers completed surveys reporting on their own FGC experiences and those of their daughters’ and on their educational history and socioeconomic status.

Results

The association between MLS and daughter circumcision was weak but positive for the full sample. Contrary to predictions, in countries in which FGC is uncommon, it was more positively associated with MLS, and in countries in which it is common, it was weakly or negatively associated with MLS.

Conclusion

Results are contrary to the notion that the intergenerational transmission of FGC is a function of happiness deriving from its cultural normativity. They suggest, instead, a diversity of social motives depending on cultural context. Customised messaging to reduce the intergenerational transmission of FGC is discussed.
Prevalence of perinatal post-traumatic stress disorder (PTSD) in low-income and middle-income countries: a systematic review and meta-analysis
Authors: Jenkins Holly , Daskalopoulou Zoe , Opondo Charles , Alderdice Fiona , Fellmeth Gracia
Published: May 2024

Objectives

To systematically synthesise the evidence on prevalence of perinatal post-traumatic stress disorder (PTSD) in low-income and middle-income countries (LMICs).

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, Embase, PsycINFO, Scopus, Web of Science, Global Health, Global Index Medicus and the grey literature were searched with no language or date restrictions. The final search was carried out on 3 May 2022.

Eligibility criteria

Cross-sectional, cohort or case–control studies that assessed the prevalence of PTSD in pregnant or postpartum women in LMICs were included.

Data extraction and synthesis

Screening, data extraction and quality assessment were conducted independently by two reviewers. Pooled prevalence estimates were calculated with 95% CIs and prediction intervals (PI) using random-effects meta-analyses. Subgroup analyses and meta-regression were conducted to explore possible sources of statistical heterogeneity.

Results

39 studies were included in the systematic review of which 38 were included in meta-analysis. The pooled prevalence of clinically diagnosed perinatal PTSD was 4.2% (95% CI 2.2% to 6.8%; 95% PI 0–18%; 15 studies). The pooled prevalence of self-reported perinatal PTSD symptoms was 11.0% (95% CI 7.6% to 15.0%; 95% PI 0–36%; 23 studies). There was no evidence of differences in prevalence according to perinatal stage (antenatal versus postnatal), geographical region, type of setting or study quality.

Conclusions

Findings of this review suggest 1 in 10 perinatal women experiences symptoms of PTSD and 1 in 20 experiences clinically diagnosed PTSD. Statistical heterogeneity between studies persisted in subgroup analyses and results should be interpreted with caution. More research from low-income countries is needed to improve understanding of the burden of perinatal PTSD in these settings.

PROSPERO registration number

CRD42022325072.
Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target
Authors: Ford Alexander C , Staudacher Heidi M , Talley Nicholas J
Published: May 2024

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.
Diagnostic yield from symptomatic gastroscopy in the UK: British Society of Gastroenterology analysis using data from the National Endoscopy Database
Authors: Beaton David Robert , Sharp Linda , Lu Liya , Trudgill Nigel J , Thoufeeq Mo , Nicholson Brian D , Rogers Peter , Docherty James , Jenkins Anna , Morris Allan John , Rösch Thomas , Rutter Matthew D
Published: May 2024

Objective

This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation.

Design

A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett’s oesophagus (BO) diagnosis). Adjusted positive predictive values (aPPVs) were calculated.

Results

382 370 diagnostic gastroscopies were analysed; 30.4% were performed in patients aged <50 and 57.7% on female patients. The overall unadjusted PPV for cancer was 1.0% (males 1.7%; females 0.6%, p<0.01). Other major pathology was found in 9.1% of procedures, whereas 89.9% reported only normal findings or minor pathology (92.5% in females; 94.6% in patients <50).

Highest cancer aPPVs were reached in the over 50s (1.3%), in those with dysphagia (3.0%) or weight loss plus another symptom (1.4%). Cancer aPPVs for all other symptoms were below 1%, and for those under 50, remained below 1% regardless of symptom. Overall, 73.7% of gastroscopies were carried out in patient groups where aPPV cancer was <1%.

The overall unadjusted PPV for BO was 4.1% (males 6.1%; females 2.7%, p<0.01). The aPPV for BO for reflux was 5.8% and ranged from 3.2% to 4.0% for other symptoms.

Conclusions

Cancer yield was highest in elderly male patients, and those over 50 with dysphagia. Three-quarters of all gastroscopies were performed on patients whose cancer risk was <1%, suggesting inefficient resource utilisation.