bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Body Weight and Leukopenia in Non‐Kidney Solid Organ Transplant Recipients With Normal Renal Function Who Are Receiving Valganciclovir for CMV Prophylaxis
Authors: Haddad Sara , Dee Kevin , Chiang Augusto Dulanto , Feller Fionna , Ding Tan , Ayers Gregory D. , Potts Marissa , LaRue Richard W.
Published: December 2024

Background

Cytomegalovirus (CMV) disease causes significant morbidity among solid organ transplant (SOT) recipients. To prevent CMV disease, eligible recipients are frequently started on valganciclovir (VGC) prophylaxis post‐transplant. Leukopenia has been documented as a primary adverse events of the drug (1). This study's primary aim was to determine whether a patient's weight at the start of VGC prophylaxis was associated with the development of leukopenia.

Methods

This was a single center, retrospective cohort study that included adults > 18 years of age, who had received an organ transplant (heart, liver, or lung) at an academic transplant center from January 1, 2018 through December 31, 2022. A creatinine clearance of > 60 mL/min was required.

Results

All 294 included patients received 900 mg/day of VGC for CMV prophylaxis, without dose adjustment. Fifty‐two percent of the patients developed leukopenia while receiving VGC prophylaxis. The mean weight at initiation of VGC was higher in patients who did not develop leukopenia (97.9 kg) compared to those who did (90.7 kg; p = 0.0112). It was found that with each 1 kg increase in body weight, the likelihood of developing leukopenia decreased by 1.7% (p = 0.004, odds ratio = 0.983, 95% confidence interval [CI], 0.972–0.994). Patients with a baseline body‐mass index (BMI) > 25 had a longer median freedom time from leukopenia after initiation of VGC as compared to the group with baseline BMI < 25 (log‐rank p = 0.035).

Conclusion

These data suggest that in SOT recipients with normal renal function, receiving a fixed dose of VGC resulted in a significant, inverse relationship between body weight and the development of leukopenia.
Nosotros, ampliamente confirmados : Erección de la Provincia Colombiana de la Compañía de Jesús (1922-1924)
Authors:   Pontificia Universidad Javeriana, Bayona Zamora, S. J. Jairo Gilberto
Published: December 2024

Este libro se realizó en el contexto de la celebración de los cien años de creación de la Provincia Colombiana de la Compañía de Jesús, la cual fue erigida por el padre general Wlodomiro Ledóchowski por el Decreto del 9 de septiembre de 1924, en la fiesta de san Pedro Claver. Con un estudio profundo de fuentes primarias, en los archivos de la Compañía en Roma y Bogotá, este libro muestra que la Provincia Colombiana no se erigió por la exigencia autoritaria de la obediencia, sino por una obediencia discernida y un proceso consultivo del Instituto de la Compañía y del conjunto de jesuitas involucrado en la toma de decisión en Roma, España y Colombia. En esta medida, la erección de la Provincia Colombiana de la Compañía de Jesús es un ejemplo singular de cómo el carisma del fundador, san Ignacio de Loyola, se transforma en estructuras sociales, a través de un ejercicio de corresponsabilidad que conecta iniciativas individuales con el vigoroso aparato institucional de la Orden. En este sentido, emerge una perspectiva novedosa de aproximación a la historia de la Compañía, que pone el énfasis en la dimensión consultiva de su gobierno y se centra menos en el imaginario de una orden administrada por una jerarquía monolítica estrictamente piramidal y centralizada. Este libro es también un gesto de agradecimiento a todos los que han hecho parte de esta historia.
Comparing neural networks against click train detectors to reveal temporal trends in passive acoustic sperm whale detections
Authors: Garrobé Fonollosa Laia , Webber Thomas , Brotons José Maria , Cerdà Margalida , Gillespie Douglas , Pirotta Enrico , Rendell Luke
Published: December 2024

Passive acoustic monitoring (PAM) is an increasingly popular tool to study vocalising species. The amount of data generated by PAM studies calls for robust automatic classifiers. Deep learning (DL) techniques have been proven effective in identifying acoustic signals in challenging datasets, but due to their black-box nature their underlying biases are hard to quantify. This study compares human analyst annotations, a multi-hypothesis tracking (MHT) click train classifier and a DL-based acoustic classifier to classify acoustic recordings based on the presence or absence of sperm whale (Physeter macrocephalus) click trains and study the temporal and spatial distributions of the Mediterranean sperm whale subpopulation around the Balearic Islands. The MHT and DL classifiers showed agreements with human labels of 85.7% and 85.0%, respectively, on data from sites they were trained on, but both saw a drop in performance when deployed on a new site. Agreement rates between classifiers surpassed those between human experts. Modeled seasonal and diel variations in sperm whale detections for both classifiers showed compatible results, revealing an increase in occurrence and diurnal activity during the summer and autumn months. This study highlights the strengths and limitations of two automatic classification algorithms to extract biologically useful information from large acoustic datasets.
Terrestrial evidence for volcanogenic sulfate-driven cooling event ~30 kyr before the Cretaceous–Paleogene mass extinction
Authors: O’Connor Lauren K. , Jerrett Rhodri M. , Price Gregory D. , Lyson Tyler R. , Lengger Sabine K. , Peterse Francien , van Dongen Bart E.
Published: December 2024

Alongside the Chicxulub meteorite impact, Deccan volcanism is considered a primary trigger for the Cretaceous–Paleogene (K–Pg) mass extinction. Models suggest that volcanic outgassing of carbon and sulfur—potent environmental stressors—drove global temperature change, but the relative timing, duration, and magnitude of such change remains uncertain. Here, we use the organic paleothermometer MBT′
5me
and the carbon-isotope composition of two K–Pg-spanning lignites from the western Unites States, to test models of volcanogenic air temperature change in the ~100 kyr before the mass extinction. Our records show long-term warming of ~3°C, probably driven by Deccan CO
2
emissions, and reveal a transient (<10 kyr) ~5°C cooling event, coinciding with the peak of the Poladpur “pulse” of Deccan eruption ~30 kyr before the K–Pg boundary. This cooling was likely caused by the aerosolization of volcanogenic sulfur. Temperatures returned to pre-event values before the mass extinction, suggesting that, from the terrestrial perspective, volcanogenic climate change was not the primary cause of K–Pg extinction.
An agile multimodal microrobot with architected passively morphing wheels
Authors: Lai Yuchen , Zang Chuanqi , Luo Guoquan , Xu Shiwei , Bo Renheng , Zhao Jianzhong , Yang Youzhou , Jin Tianqi , Lan Yu , Wang Yuejiao , Wen Li , Pang Wenbo , Zhang Yihui
Published: December 2024

Multimodal microrobots are of growing interest due to their capabilities to navigate diverse terrains, with promising applications in inspection, exploration, and biomedicine. Despite remarkable progress, it remains challenging to combine the attributes of excellent maneuverability, low power consumption, and high robustness in a single multimodal microrobot. We propose an architected design of a passively morphing wheel that can be stabilized at distinct geometric configurations, relying on asymmetric bending stiffness of bioinspired tentacle structures. By integrating such wheels with electromagnetic motors and a flexible body, we develop a highly compact, lightweight, multimodal microrobot (length ~32 mm and mass ~4.74 g) with three locomotion gaits. It has high motion speed (~21.2 BL/s), excellent agility (relative centripetal acceleration, ~206.9 BL/s
2
), low power consumption (cost of transport, ~89), high robustness, and strong terrain adaptabilities. Integration of batteries and a wireless control module enables developments of an untethered microrobot that maintains high motion speed and excellent agility, with capabilities of traveling in hybrid terrains.
Metabolomic age (MileAge) predicts health and life span: A comparison of multiple machine learning algorithms
Authors: Mutz Julian , Iniesta Raquel , Lewis Cathryn M.
Published: December 2024

Biological aging clocks produce age estimates that can track with age-related health outcomes. This study aimed to benchmark machine learning algorithms, including regularized regression, kernel-based methods, and ensembles, for developing metabolomic aging clocks from nuclear magnetic resonance spectroscopy data. The UK Biobank data, including 168 plasma metabolites from up to
N
= 225,212 middle-aged and older adults (mean age, 56.97 years), were used to train and internally validate 17 algorithms. Metabolomic age (MileAge) delta, the difference between metabolite-predicted and chronological age, from a Cubist rule–based regression model showed the strongest associations with health and aging markers. Individuals with an older MileAge were frailer, had shorter telomeres, were more likely to suffer from chronic illness, rated their health worse, and had a higher all-cause mortality hazard (HR = 1.51; 95% CI, 1.43 to 1.59;
P
< 0.001). This metabolomic aging clock (MileAge) can be applied in research and may find use in health assessments, risk stratification, and proactive health tracking.
AI-driven universal lower-limb exoskeleton system for community ambulation
Authors: Lee Dawit , Lee Sanghyub , Young Aaron J.
Published: December 2024

Exoskeletons offer promising solutions for improving human mobility, but a key challenge is ensuring the controller adapts to changing walking conditions. We present an artificial intelligence (AI)–driven universal exoskeleton system that dynamically switches assistance types between walking modes, modulates assistance levels corresponding to the ground slope, and delivers assistance timely based on the current gait phase in real-time. During treadmill validation, AI-based assistance reduced metabolic cost by 6.5% compared to 3.5% for conventional assistance. We expanded testing the controller in real-world walking, where AI-based assistance showed effective modulation and higher user preference compared to conventional assistance. Leveraging the AI-based approach and a comprehensive dataset, the controller achieved superior performance in environment- and user-state estimations. This approach does not require a separate mode classifier and operates on a user-independent basis, enabling immediate deployment across diverse conditions. This study highlights the potential of AI-driven exoskeletons in facilitating human locomotion in real-world ambulation.
A global comparison of surface and subsurface microbiomes reveals large-scale biodiversity gradients, and a marine-terrestrial divide
Authors: Ruff S. Emil , de Angelis Isabella Hrabe , Mullis Megan , Payet Jérôme P. , Magnabosco Cara , Lloyd Karen G. , Sheik Cody S. , Steen Andrew D. , Shipunova Anna , Morozov Aleksey , Reese Brandi Kiel , Bradley James A. , Lemonnier Clarisse , Schrenk Matthew O. , Joye Samantha B. , Huber Julie A. , Probst Alexander J. , Morrison Hilary G. , Sogin Mitchell L. , Ladau Joshua , Colwell Frederick
Published: December 2024

Subsurface environments are among Earth’s largest habitats for microbial life. Yet, until recently, we lacked adequate data to accurately differentiate between globally distributed marine and terrestrial surface and subsurface microbiomes. Here, we analyzed 478 archaeal and 964 bacterial metabarcoding datasets and 147 metagenomes from diverse and widely distributed environments. Microbial diversity is similar in marine and terrestrial microbiomes at local to global scales. However, community composition greatly differs between sea and land, corroborating a phylogenetic divide that mirrors patterns in plant and animal diversity. In contrast, community composition overlaps between surface to subsurface environments supporting a diversity continuum rather than a discrete subsurface biosphere. Differences in microbial life thus seem greater between land and sea than between surface and subsurface. Diversity of terrestrial microbiomes decreases with depth, while marine subsurface diversity and phylogenetic distance to cultured isolates rivals or exceeds that of surface environments. We identify distinct microbial community compositions but similar microbial diversity for Earth’s subsurface and surface environments.
The
Plasmodium falciparum
NCR1 transporter is an antimalarial target that exports cholesterol from the parasite’s plasma membrane
Authors: Zhang Zhemin , Lyu Meinan , Han Xu , Bandara Sepalika , Cui Meng , Istvan Eva S. , Geng Xinran , Tringides Marios L. , Gregor William D. , Miyagi Masaru , Oberstaller Jenna , Adams John H. , Zhang Youwei , Nieman Marvin T. , von Lintig Johannes , Goldberg Daniel E. , Yu Edward W.
Published: December 2024

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria,
Plasmodium falciparum
, has developed resistance to nearly all currently available antimalarial drugs. The
P. falciparum
Niemann-Pick type C1–related (PfNCR1) transporter has been identified as a druggable target, but its structure and detailed molecular mechanism are not yet available. Here, we present three structures of PfNCR1 with and without the functional inhibitor MMV009108 at resolutions between 2.98 and 3.81 Å using single-particle cryo–electron microscopy (cryo-EM), suggesting that PfNCR1 binds cholesterol and forms a cholesterol transport tunnel to modulate the composition of the parasite plasma membrane. Cholesterol efflux assays show that PfNCR1 is an exporter capable of extruding cholesterol from the membrane. Additionally, the inhibition mechanism of MMV009108 appears to be due to a direct blockage of PfNCR1, preventing this transporter from shuttling cholesterol.
Regional differences in three-dimensional fiber organization, smooth muscle cell phenotype, and contractility in the pregnant mouse cervix
Authors: Hansen Christopher J. , Rogers Jackson H. , Brown Alexus J. , Boatwright Naoko , Siricilla Shajila , O’Brien Christine M. , Panja Sourav , Nichols Cameron M. , Devanathan Kanchana , Hardy Benjamin M. , Does Mark D. , Anderson Adam W. , Paria Bibhash C. , Mahadevan-Jansen Anita , Reese Jeff , Herington Jennifer L.
Published: December 2024

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous contractions, distension had a minimal effect on contractility, and the upper cervix had forceful contractions in response to labor-inducing agents (oxytocin and prostaglandin E
2
). These findings identify regional differences in cervix contractility related to contractile SMC content and fiber organization, which could be targeted with diagnostic technologies and for therapeutic intervention.
Chiral flat-band optical cavity with atomically thin mirrors
Authors: Suárez-Forero Daniel G. , Ni Ruihao , Sarkar Supratik , Jalali Mehrabad Mahmoud , Mechtel Erik , Simonyan Valery , Grankin Andrey , Watanabe Kenji , Taniguchi Takashi , Park Suji , Jang Houk , Hafezi Mohammad , Zhou You
Published: December 2024

A fundamental requirement for photonic technologies is the ability to control the confinement and propagation of light. Widely used platforms include two-dimensional (2D) optical microcavities in which electromagnetic waves are confined in either metallic or distributed Bragg reflectors. Recently, transition metal dichalcogenides hosting tightly bound excitons with high optical quality have emerged as promising atomically thin mirrors. In this work, we propose and experimentally demonstrate a subwavelength 2D nanocavity using two atomically thin mirrors with degenerate resonances. Angle-resolved measurements show a flat band, which sets this system apart from conventional photonic cavities. We demonstrate how the excitonic nature of the mirrors enables the formation of chiral and tunable optical modes upon the application of an external magnetic field. Moreover, we show the electrical tunability of the confined mode. Our work demonstrates a mechanism for confining light with high-quality excitonic materials, opening perspectives for spin-photon interfaces, and chiral cavity electrodynamics.
Solvent-responsive covalent organic framework membranes for precise and tunable molecular sieving
Authors: Yang Hao , Zhang Haoyuan , Kang Chengjun , Ji Chunqing , Shi Dongchen , Zhao Dan
Published: December 2024

Membrane-based nanofiltration has the potential to revolutionize the large-scale treatment of organic solvents in various applications. However, the widely used commercial membranes suffer from low permeability, narrow structural tunability, and limited chemical resistance. Here, we report a strategy for fabricating covalent organic framework (COF) membranes with solvent-responsive structural flexibility. The interlayer shifting of these COF membranes in polar organic solvents results in sub-nanopores with high selectivity. High rejection rates (>99%), high permeance (>15 kilogram meter
−2
hour
−1
bar
−1
), and excellent organic solvent resistance of these smart COF membranes are achieved for a diverse array of nanofiltration applications.
Reactive vapor-phase dealloying-alloying turns oxides into sustainable bulk nano-structured porous alloys
Authors: Wei Shaolou , Ma Yan , Raabe Dierk
Published: December 2024

For millennia, alloying has been the greatest gift from metallurgy to humankind: a process of mixing elements, propelling our society from the Bronze Age to the Space Age. Dealloying, by contrast, acts like a penalty: a corrosive counteracting process of selectively removing elements from alloys or compounds, degrading their structural integrity over time. We show that when these two opposite metallurgical processes meet in a reactive vapor environment, profound sustainable alloy design opportunities become accessible, enabling bulk nanostructured porous alloys directly from oxides, with zero carbon footprint. We introduce thermodynamically well-grounded treasure maps that turn the intuitive opposition between alloying and dealloying into harmony, facilitating a quantitative approach to navigate synthesis in such an immense design space. We demonstrate this alloy design paradigm by synthesizing nanostructured Fe-Ni-N porous martensitic alloys fully from oxides in a single solid-state process step and substantiating the critical kinetic processes responsible for the desired microstructure.
Moo19 and B2: Structures of
Schitoviridae
podophages with
T
= 9 geometry and tailspikes with esterase activity
Authors: Subramanian Sundharraman , Bergland Drarvik Silje M. , Tinney Kendal R. , Doore Sarah M. , Parent Kristin N.
Published: December 2024

Podophages are, by far, the least well studied of all the bacteriophages. Despite being classified together due to their short, noncontractile tails, there is a huge amount of diversity among members of this group. Of the podophages, the N4-like
Schitoviridae
family is the least well studied structurally and is quite divergent from well-characterized podophages such as T7 and P22. In this work, we isolate and fully characterize two members of the
Schitoviridae
family by cryo–electron microscopy, genetics, and biochemistry. We describe the capsid features of Moo19 and B2, including a decoration protein. In addition, we have fully modeled the tail machinery for both phages and identify proteins with esterase activity. Genetic knockouts of the host reveal factors specific for host attachment including key modifications to the O-antigen on the lipopolysaccharide. Moo19 and B2 are both
Schitoviridae
members, yet some distinct differences in the genome and structure place them into distinct clades.
Even teleoperated robots are discriminated against in science fictions
Authors: Murphy Robin R.
Published: December 2024

A robot body is not a shield from discrimination in John Scalzi’s science fiction novel
Head On.
IFN-γ–producing T
H
1 cells and dysfunctional regulatory T cells contribute to the pathogenesis of Sjögren’s disease
Authors: Wang Yin-Hu , Li Wenyi , McDermott Maxwell , Son Ga-Yeon , Maiti George , Zhou Fang , Tao Anthony Y. , Raphael Dimitrius , Moreira Andre L. , Shen Boheng , Vaeth Martin , Nadorp Bettina , Chakravarti Shukti , Lacruz Rodrigo S. , Feske Stefan
Published: December 2024

Sjögren’s disease (SjD) is an autoimmune disorder characterized by progressive salivary and lacrimal gland dysfunction, inflammation, and destruction, as well as extraglandular manifestations. SjD is associated with autoreactive B and T cells, but its pathophysiology remains incompletely understood. Abnormalities in regulatory T (T
reg
) cells occur in several autoimmune diseases, but their role in SjD is ambiguous. We had previously shown that the function and development of T
reg
cells depend on store-operated Ca
2+
entry (SOCE), which is mediated by ORAI1 Ca
2+
channels and stromal interaction protein 1 (STIM1) and STIM2. Here, we show that mice with a Foxp3
+
T
reg
cell–specific deletion of
Stim1
and
Stim2
develop a phenotype that fulfills all classification criteria of human SjD. Mutant mice have salivary and lacrimal gland inflammation characterized by strong lymphocyte infiltration and transcriptional signatures dominated by T helper 1 (T
H
1) and interferon (IFN) signaling. CD4
+
T cells from mutant mice are sufficient to induce SjD-like disease in an IFN-γ–dependent manner. Inhibition of IFN signaling with the JAK1/2 inhibitor baricitinib alleviated CD4
+
T cell–induced SjD in mice. These findings are consistent with the transcriptional profiles of CD4
+
T cells from patients with SjD, which indicate enhanced T
H
1 but reduced memory T
reg
cell function. Together, our study provides evidence for a critical role of dysfunctional T
reg
cells and IFN-γ–producing T
H
1 cells in the pathogenesis of SjD.
Genital bleeding in prepubertal girls: a systematic review
Authors: Moore Yasmin , Hopkinshaw Bryony , Arrowsmith Briony , White Catherine , Gabriel Lily
Published: December 2024

Introduction

This systematic review aims to collate evidence of the causes of genital bleeding, other than child sexual abuse and accidental injuries, presenting in prepubertal girls. It provides an update to the 2015 Royal College of Paediatrics and Child Health publication ‘The Physical Signs of Child Sexual Abuse’, an evidence-based review also known as the Purple Book.

Methods

MEDLINE, EMBASE and Scopus databases were searched for studies published between March 2014 and June 2023. Eligible studies were primary studies reporting on genital bleeding with extractable data for prepubertal girls.

Results

99 studies, describing a total of 672 prepubertal girls, met the inclusion criteria. The most common medical conditions with genital bleeding as a presenting feature were lichen sclerosus, infections and infestations, hormonal causes, urethral prolapse, vaginal foreign bodies and tumours. Meta-analysis was not possible due to the large heterogeneity of the studies.

Conclusion

This review added further evidence to the 2015 edition of the Purple Book, describing the multiple medical conditions that may present with genital bleeding. Several of these conditions can mimic the presentation of child sexual abuse or may coexist with child sexual abuse.
Mondor disease
Authors: B M Nandakumar , Hiremath Bharati , Vinaya Kumar Harshinie
Published: December 2024

Mondor disease (MD) is a benign inflammatory disorder of the veins over the thoracoabdominal wall. Although the disease has been described for a century, very few descriptions in literature are available. This is due to a lack of awareness among treating physicians about the disease entity as well as the self-limiting course of the disease. Patients usually present with a painful lesion in the lateral thoracic wall or as a palpable cord in the late resolving stages. The disease usually resolves with non-steroidal anti-inflammatory drugs and supportive therapy. Few patients with symptomatic tender cords require surgical excision or release. Recent studies have noted association with breast cancer, and an increase in incidence was noted in the COVID-19 pandemic. We report a woman in her 40s who presented with a band in her right lateral chest wall for 6 months and was diagnosed with MD. She underwent an excision and is currently symptom free.
Enterococcusnecrotising fasciitis of the face after minor trauma presenting as periorbital cellulitis
Authors: Mudhol Rekha Ramesh , Lingamaneni Sneha , Sheelin Shruti , Vallabha Aniketan
Published: December 2024

Necrotising fasciitis (NF), commonly referred to as ‘flesh-eating disease’, is a rare but life-threatening infection. It rapidly affects subcutaneous tissue, leading to necrosis of the overlying skin. Though primarily seen in the abdomen, perineum and lower limbs, periorbital involvement is rare. This case report presents an elderly male with periorbital NF following a minor head injury. The patient presented with bilateral periorbital swelling, purulent discharge and necrotic tissue. Microbiological analysis revealed a rareEnterococcusspecies as the causative pathogen. MRI and microbiological analysis confirmed the diagnosis. Treatment included intravenous antibiotics, surgical debridement and skin grafting. The patient showed significant improvement post-treatment. This case underscores the importance of prompt diagnosis and treatment to prevent severe complications.
Severe hypophosphataemia and hypocalcaemia following intravenous ferric derisomaltose and denosumab administration
Authors: Kritzinger Justin , Wyse Jonathan , Karaplis Andrew
Published: December 2024

Serum calcium and phosphorus levels are tightly regulated by the calciotropic hormone parathyroid hormone, fibroblast growth factor 23 and 1,25(OH)2vitamin D. Commonly prescribed therapies for iron-deficiency anaemia (IDA) such as ferric carboxymaltose and ferric derisomaltose (FDM) have been shown to disrupt phosphorus homeostasis, resulting in hypophosphataemia. Similarly, denosumab use can result in hypocalcaemia due to the inhibition of osteoclastic maturation, activity and survival. Here, we report the development of severe hypophosphataemia and hypocalcaemia in a patient with osteoporosis and IDA following treatment with denosumab and FDM. The patient remained asymptomatic; however, supplementation with calcium, phosphorus and calcitriol replacement was required prior to eventual normalisation of serum levels. Often concomitantly prescribed, little guidance exists regarding electrolyte disturbances following the administration of FDM and denosumab. While hypophosphataemia and hypocalcaemia are relatively uncommon when prescribed individually, synergistic effects likely exist that warrant regular monitoring and occasional supplementation.
Metastatic conjunctival melanoma: a multicentre international study
Authors: Jain Puneet , Finger Paul T , Filì Maria , Damato Bertil , Coupland Sarah E , Heimann Heinrich , Kenawy Nihal , Brouwer Niels J , Marinkovic Marina , van Duinen Sjoerd , Caujolle Jean-Pierre , Maschi Celia , Seregard Stefan , Pelayes David E , Folgar Martin , Yousef Yacoub , Krema Hatem , Gallie Brenda , Calle Vasquez Carlos Alberto
Published: December 2024

Background

To reveal clinical findings related to metastatic conjunctival melanoma.

Methods

10 ophthalmic oncology centres (9 countries and 4 continents) shared data to create a large clinical case series. The main outcome measures were the incidence and cumulative risk of systemic metastasis, study mortality rates and Kaplan-Meier patient mortality after developing conjunctival melanoma metastasis.

Results

Of 288 patients, 29 developed metastasis. Five had metastasis at presentation, were American Joint Committee on Cancer (AJCC) cT3-category and exhibited tumour-surface ulceration. Four of five (80%) had melanotic tumours with plical and/or caruncular involvement and died within 1 year. One survived 21 months. In contrast, 24 developed metastases during follow-up (mean 4.6±3.2 years). Their primary tumours were cT1 (n=13/24, 54.1%), cT2 (n=6/24, 25%), cT3 (n=2/24, 8.3%) and 3 cTx (12.5%) at presentation. Death had occurred in 17 patients (n=17/24, 71%) by the end of the study. The cumulative risk of systemic metastasis after treatment was 0.4% (95% CI 0.6% to 2.9%) at 1 year, 8.6% (95% CI 5.1% to 14.3%) at 5 years and 22.3% (95% CI 14.5% to 33.5%) at 10 years. Each increase in AJCC cT category was associated with an 89% higher risk for metastasis (HR=1.89, p<0.001). Among all 29 patients who developed metastasis, those who presented with AJCC cT3 disease were at highest risk (p<0.001). Liver and lung (n=13 each) were the most reported metastatic sites.

Conclusion

Metastatic conjunctival melanoma was found in 10% of conjunctival melanoma patients. Tumour-specific characteristics including AJCC cT3-category, conjunctival location and surface ulceration were associated with metastatic risk. Survival durations were shorter for those presenting with metastasis.
Sonographic bleb visualisation after PAUL glaucoma implant surgery
Authors: Weber Constance , Weinhold Leonie , Walz Wolfgang , Petrak Michael , Holz Frank G , Liegl Raffael , Mercieca Karl
Published: December 2024

Background/aims

Bleb characteristics in the area around the plate following glaucoma drainage device (GDD) surgery are difficult to evaluate on slit lamp examination. Ultrasound sonography could be used for more detailed visualisation. The aim of this study was to describe bleb configuration after PAUL glaucoma implant (PGI) surgery and evaluate the possible correlation with intraocular pressure (IOP) in order to derive new markers for evaluating GDD function.

Methods

Patients underwent a 15 MHz ultrasound examination (Compact Touch, Quantel Medical) after undergoing PGI implantation. The filtering bleb dimensions were measured and bleb configuration was assessed along with documentation of all clinical data.

Results

A total of 70 eyes from 65 patients were included. 55 eyes (78.6%) had a double-layered bleb whereas 15 eyes (21.4%) had a bleb with only one compartment (six eyes, 8.6% above; nine eyes, 12.9% below the plate). The total height of both compartments averaged 3.52 mm. The average IOP was 13.03 mm Hg. There was a significant correlation between single and double-layered blebs (p<0.01) with regard to IOP (one compartment: 16.47 mm Hg vs two compartments: 12.09 mm Hg). There was no significant correlation between total bleb height (p=0.143) or bleb extension (T: p=0.629; L: p=0.742). However, total bleb height showed an inverse association with IOP. Blebs with a height >2 mm had significantly lower mean IOP than those having <2 mm bleb heights (p=0.041).

Conclusions

Sonography is a suitable modality to evaluate bleb characteristics after PGI implantation. Blebs with a double fluid layer are significantly correlated with lower IOP values. Bleb height has an inverse association with IOP, with higher blebs (>2 mm) showing a significantly lower IOP.
Medication use and risk of reflux oesophagitis
Authors: Ueta Ren , Komori Shiori , Umemoto Kumiko , Hata Masahiro , Masuda Erika , Seto Kana , Nishiie Yuriko , Suzuki Keigo , Hisada Yuya , Yanai Yuka , Otake Yuki , Okubo Hidetaka , Watanabe Kazuhiro , Akazawa Naoki , Yokoi Chizu , Akiyama Junichi
Published: December 2024

Objective

Reflux oesophagitis (RO) is one of the most common diseases encountered by gastroenterologists and primary care physicians. However, few epidemiological studies have investigated the association of medication use and RO. This study aimed to investigate the prevalence of RO and its risk factors, particularly with respect to medication use.

Methods

This retrospective, cross-sectional study included consecutive patients who underwent oesophagogastroduodenoscopy (OGD) and were assessed using questionnaires at the National Center for Global Health and Medicine (Shinjuku, Tokyo, Japan) between October 2015 and December 2021. The questionnaire collected data on patient characteristics, medical history, smoking and alcohol consumption, and medications that patients were taking at the time of OGD.

Results

Among the 13 993 eligible patients, the prevalence of RO was 11.8%. Multivariate logistic regression analysis indicated that male sex (OR=1.52 (95% CI 1.35 to 1.72), p<0.001); obesity (OR=1.57 (95% CI 1.40 to 1.77), p<0.001); smoking (OR=1.19 (95% CI 1.02 to 1.38), p=0.026); alcohol consumption (OR=1.20 (95% CI 1.07 to 1.35), p=0.002); diabetes (OR=1.19 (95% CI 1.02 to 1.39), p=0.029); hiatal hernia (OR=3.10 (95% CI 2.78 to 3.46), p<0.001); absence of severe gastric atrophy (OR=2.14 (95% CI 0.39 to 0.56), p<0.001); and the use of calcium channel blockers (CCBs) (OR=1.22 (95% CI 1.06 to 1.40), p=0.007), theophylline (OR=2.13 (95% CI 1.27 to 3.56), p=0.004), and non-steroidal anti-inflammatory drugs (NSAIDs) (OR=1.29 (95% CI 1.03 to 1.61), p=0.026) were independent predictors of RO.

Conclusion

RO was present in 11.8% of patients. Use of CCBs, theophylline, and NSAIDs were independent predictors of RO.
Epidemiology of chronic and acute pancreatitis in India (EPICAP-India): protocol for a multicentre study
Authors: Krishnan Anand , Pillai Divya , Amarchand Ritvik , Agarwal Ashish , Ahuja Vineet , Baloni Vineeta , Basu Subhra Samujjwal , Bhardwaj Pankaj , Choudhury Bikash , Chowdhury Sudipta Dhar , Dabar Deepti , Das Soumi , Deshmukh Pradeep , Devadas Krishnadas , Dhali Gopal Krishna , Gunjan Deepak , Gupta Anmol , Jain Saransh , Kedia Saurabh , Kumar Rakesh , Kumar Sanjeev , Makharia Govind K , Monga Nitika , Rungta Sumit , Saraya Anoop , Sarkar Rajib , Shalimar  , Sharma Brij , Singh Shivendra , Sujatha Chintha , Wadhwa Nitya , Garg Pramod Kumar
Published: December 2024

Introduction

Acute and chronic pancreatitis (CP) are inflammatory conditions of the pancreas that cause local and systemic complications. The epidemiology of these conditions are not well-known in India.

Methods and analysis

We describe the protocol and procedures of a multicentre study for delineating the epidemiology of pancreatitis in India. We plan to cover 110 000 people across 10 geographically distributed sites in 10 states of India to estimate the burden and risk factors of CP. Trained investigators will make house visits and screen for abdominal pain requiring hospitalisation or pre-diagnosed CP. The screened positive participants will be reviewed by a gastroenterologist to confirm the diagnosis of CP based on radiological imaging. For each case, four controls will be selected and data on risk factors for CP (tobacco, alcohol, family history, metabolic causes) and blood for genetic markers will be collected. Information on the cost of treatment and quality of life will be collected from patients with CP. For estimating incidence of acute pancreatitis (AP), hospital-based sentinel surveillance will be conducted in 10 districts across these 10 states. All hospitals in the district will be contacted to provide a line list of admissions due to acute abdomen including AP for 2 years. The spread of acute abdomen cases will be used to define the catchment area and estimate the denominator population. The line-listed cases with AP living in the catchment area will form the numerator to calculate the incidence. The study will provide critical information for planning pancreatitis-related services in the country.

Ethics and dissemination

The institutional ethics committee (IECs) at all the participating sites have given their approval for the study. All the participants whose data will be collected will be included after written informed consent. The results may be presented at national or international conferences and will be reported in peer-reviewed publications.
A qualitative study of the government’s engagement of the private health sector in the delivery of Ghana’s COVID-19 emergency response
Authors: Abekah-Nkrumah Gordon , Abor Patience Aseweh , Addai Frimpong Kingsley , Martey Maureen M , Asrat Sofonias Getachew , Kasolo Francis Chisaka
Published: December 2024

Introduction

There is a growing literature on the significance of private sector engagement and collaboration for optimal response to health emergencies. The current study examines how the private sector was engaged by the Ghanaian government to implement effectively the national COVID-19 emergency response.

Methods

The study drew on a qualitative research design, interviewing 20 respondents in 15 unique organisations. Interviews were recorded, transcribed and analysed using a thematic analytical approach.

Findings

The findings of the study suggest that the government demonstrated leadership in mobilising, resourcing, and collaborating with the private health sector to deliver its pandemic response via a defined emergency response plan, a coordinated pandemic response structure and a robust platform for information gathering and sharing. However, the government fell short of providing the enabling environment for the private health sector to expand their capacity to meet increased demand for health services during the pandemic. There were also challenges related to the over concentration of resources in the public health response and national level structures to the detriment of clinical care and sub-national level structures. Generally, the findings also indicate a fragmented private health sector that is not only unattractive for the government to engage and collaborate with, but also weak in terms of capacity (financial and human resources) to partner government and respond to any major health emergency.

Conclusion

There is a need for policymakers to put in place an appropriate policy framework that will help in organising, engaging and collaborating with private health entities. The gaps identified and lessons learnt from implementing the pandemic response should be addressed as a matter of urgency to improve the readiness of Ghana’s health system for future health emergencies.
Changing power narratives: an exemplar case study on the professionalisation of community health workers in Liberia
Authors: Neumann Anne , Subah Marion , van der Westhuizen Helene-Mari
Published: December 2024

Despite their central role in achieving health equity and Universal Health Coverage, only a minority of community health workers (CHWs) is formally recognised as health workforce and receives a salary. Community health policies are formed within the power dynamics of global health practice. We argue that critical investigations of the power dynamics that influence the design of CHW programmes can contribute system-level insights to strengthen their roles.

We present a national-level case study of the Liberian Community Health Assistant programme as an exemplar case of successfully introducing a nationwide CHW policy that professionalises CHWs. Using a theory of how power is exercised (Steven Lukes) for our analysis, we argue that Liberia’s success in overcoming external funder push-back on the payment of CHWs was enabled by strong political commitment and (re-)claiming government authority in and outside of decision-making processes. Consensus-building across government departments strengthened the government’s decision-making power. The availability and strategic use of suitable and contextualised evidence focused on the rights of CHWs allowed for proactive engagement with external funders’ concerns. To draw on learnings from the experience of Liberia, we recommend looking beyond the common effectiveness-oriented narratives in academic literature that focus on CHW’s functional role. By focussing on how power is exerted through policy negotiations around professionalisation, it could be possible to reframe conventional approaches to the role of CHW in other contexts as well.
Association of social vulnerability and depression incidence post intracerebral haemorrhage: a cohort study
Authors: Popescu Dominique Lynn , Abramson Jessica , Keins Sophia , Mallick Akashleena , Kourkoulis Christina , Anderson Christopher D , Rosand Jonathan , Biffi Alessandro , Yechoor Nirupama
Published: December 2024

Objectives

Survivors of intracerebral haemorrhage (ICH) are at high risk of incident depression, which is modified by social determinants of health (SDOH) and associated with worse functional outcomes. We sought to determine the role of prestroke SDOH in depression incidence after ICH to better characterise post-ICH outcomes.

Study design

We analysed data from a cohort study of ICH survivors without prestroke depression, presenting at Massachusetts General Hospital between 2006 and 2017. We collected information from electronic health records (EHR), follow-up interviews and CT/MRI. The relationship between social vulnerability, air quality and post-ICH depression incidence within 12 months of acute haemorrhage was investigated using logistic regression models that also included EHR and CT/MRI information as predictors.

Results

Participants were 576 survivors, median age of 72 (IQR=61–81), 317 (55%) self-reported as male and 482 (84%) as white. 204 (35%) were diagnosed with depression within 12 months of ICH. Hospital admission longer than 1 week (OR 1.80, 95% CI 1.08 to 3.00), cerebral amyloid angiopathy (CAA) burden (OR 1.45, 95% CI 1.25 to 1.68) and social vulnerability (OR 3.03, 95% CI 1.49 to 6.19) were associated with depression incidence post-ICH.

Conclusions

In addition to CAA burden and patient location 1-week post-ICH, social vulnerability was independently associated with depression among ICH survivors. Our findings suggest that social vulnerability influences ICH outcomes. Future studies should investigate how poststroke clinical care interventions can address SDOH effects to reduce incident depression and improve outcomes among ICH survivors.
An updated systematic review and meta-analysis exploring the efficacy and safety of dimethyl fumarate (DMF) for patients with multiple sclerosis (MS)
Authors: Ali Hossam Tharwat , Yousef Amr Mahmoud , El-Farargy Sara Hosny , Abdelmonhem Ahmed Mohamed , Abouda Dalia Atef , Mahmoud Ahmed Mamdoh , Elsayed Ammar Arafat , Hassaan Hazem Khaled , Afifi Ahmed M.
Published: December 2024

Background

Dimethyl fumarate (DMF) is increasingly used in treating multiple sclerosis (MS) with controversial results of the safety and efficacy of different DMF doses. We aimed to systematically review the literature to examine the safety and efficacy of DMF for MS patients.

Methods

We searched PubMed Medline, Cochrane, Web of Science, Scopus databases and clinicaltrials.gov up to June 2023 for the published trials evaluating the use of DMF for MS in adults. All included studies were screened and abstracted independently by two authors. Efficacy and safety outcome measures were extracted. The meta-analysis was conducted using Review Manager 5.4.

Results

10 studies including eight randomised controlled trials, one open-label and one single-arm before-after study with a total population size of 4278 patients were included. DMF group showed a statistically significant reduction in the proportion of relapses compared with the control group, (OR: 0.47, 95% CI: [0.41, 0.55], p<0.00001) with no statistical differences between 240 mg two times per day and three times a day doses. Furthermore, the DMF group had a significant reduction in Gd-enhanced lesions compared with control (MD=−1.53, 95% CI: [−1.91 to –1.41], p<0.00001). Our results showed a non-significant difference in adverse events that led to discontinuation of the study with an OR of 1.29 (95% CI: [0.98, 1.71], p value=0.07).

Discussion

DMF had significant efficacy and safety compared with the control, with no difference between the DMF doses. More studies with large sample sizes and longer follow-ups are needed to detect long-term safety and efficacy.
Sintilimab plus bevacizumab followed by resection in intermediate-stage hepatocellular carcinoma: a phase Ib clinical trial with biomarker analysis
Authors: Sun Hui-Chuan , Zhu Xiao-Dong , Wang Zi-Yi , Gao Qiang , Ji Yuan , Shi Ying-Hong , Wang Xiao-Ying , Qiu Shuang-Jian , Huang Cheng , Shen Ying-Hao , Zhou Jian , Fan Jia
Published: December 2024

Objective

This phase Ib trial aimed to assess the safety and efficacy of sintilimab plus bevacizumab (sintilimab/bev), followed by resection in patients with potentially resectable intermediate-stage hepatocellular carcinoma (HCC) and explore the clinical implications of circulating tumour DNA (ctDNA) and T cell receptor (TCR) repertoire.

Methods and analysis

Eligible patients with intermediate-stage HCC received sintilimab/bev treatment. Patients with partial response or stable disease for at least two consecutive evaluations and technically resectable received hepatectomy. Postoperatively patients continued to receive sintilimab/bev until tumour recurrence or intolerable toxicities for up to 12 months. The primary endpoints were treatment safety and event-free survival (EFS). Plasma ctDNA measurements and TCR repertoire were analysed.

Results

30 patients were enrolled. 17 (56.7%) patients received liver resection. Grade 3 treatment-related adverse events occurred in seven patients (23.3%). No grade 4/5 AE or postoperative mortality was observed. The median EFS of the 30 patients was 16.3 months (95% CI 13.4 to 19.2). The 12-month and 24-month survival rates were 93.2% and 82.0%, respectively. Of the 17 patients who received hepatectomy, the median recurrence-free survival was 14.1 months (95% CI 8.9 to 19.4). A lower ctDNA measurement and higher TCR repertoire were associated with better tumour response or patients’ survival.

Conclusions

The study suggested systemic therapy with sintilimab/bev was safe and effective in patients with intermediate-stage HCC, and resection in selected patients was associated with improved survival. ctDNA measurement and TCR repertoire may help identify patients who may benefit from sintilimab/bev treatment and patients with a higher risk of tumour recurrence.

Trial registration number

NCT04843943.