bluuebunny/crossref_metadata_2025 huggingface dataset:
Study protocol of the PRINCESS trial—PReoperative INtermittent fasting versus CarbohydratE loading to reduce inSulin resiStance versus standard of care in orthopaedic patients: a randomised controlled trial
Authors: Stobbe Ayla Y , de Klerk Eline S , van Wilpe Robert , Kievit Arthur J , Choi Kee Fong , Preckel Benedikt , Hollmann Markus W , Hermanides Jeroen , van Stijn Mireille F M , Hulst Abraham H
Published: January 2025

Introduction

Surgical trauma induces a metabolic stress response, resulting in reduced insulin sensitivity and hyperglycaemia. Postoperative insulin resistance (IR) is associated with postoperative complications, and extended preoperative fasting may further aggravate the postoperative metabolic stress response. Nutritional strategies, such as carbohydrate loading (CHL), have been successfully used to attenuate postoperative IR. Recent evidence suggests that time-restricted feeding (TRF), a form of intermittent fasting, improves IR in the general population, even after a short period of TRF. We hypothesise that TRF, as well as CHL, improve postoperative IR.

Methods and analysis

This open-label, single-centre, randomised controlled trial will compare the effect of short-term preoperative TRF, CHL and standard preoperative fasting on perioperative IR. A total of 75 orthopaedic patients presenting for elective intermediate to major surgery at a Dutch academic hospital will be randomly assigned to a control group (standard preoperative fasting), a TRF group or a CHL group. The primary outcome is postoperative IR, based on the updated homeostasis model assessment of IR, on the first day after surgery. Statistical analyses are performed using Student’s t-tests or Mann-Whitney U tests.

Ethics and dissemination

The local medical ethics committee of the Amsterdam UMC, the Netherlands, approved the trial protocol in January 2023 (NL81556.018.22). No publication restrictions apply, and the results of the study will be disseminated through a peer-reviewed journal.

Trial registration number

NCT05760339.
Socioeconomic position across the life course and falls among middle- and older-aged adults: protocol for a systematic review
Authors: Smit Frerik , van Zwieten Anita , Sherrington Catherine , Franco Marcia R , Cullati Stéphane , Blyth Fiona M , Khalatbari-Soltani Saman
Published: January 2025

Introduction

Individuals experiencing disadvantaged socioeconomic positions (SEPs) may be at increased risk of falls during middle and older age, and these impacts of socioeconomic factors may vary according to the duration, timing and sequencing of exposures across the life course. However, there has not been a recent systematic review of this evidence. This study, therefore, aims to synthesise existing knowledge on the association between SEP across the life course and falls within middle- and older-aged adults.

Methods and analysis

We systematically searched for literature in three academic databases from database inception to 15 March 2024: MEDLINE (Ovid), Embase (Ovid) and PsycInfo (Ovid). The search strategy combined MeSH headings and search terms related to SEP, falls, middle- and older-aged adults and observational studies. Cohort, case-control and cross-sectional studies with mean or median participant age of >40 years, which report on the association between at least one socioeconomic indicator across the life course and one fall outcome and are published in peer-reviewed academic journals were included. No language or geographic restrictions were imposed. Titles and abstracts were screened by one reviewer with 20% of titles and abstracts also screened by a second reviewer. Two reviewers independently screened full texts. Data will be extracted using a standardised Excel template. Using a modified Quality in Prognosis Studies (QUIPS) tool, the risk of bias of included studies will be assessed by one reviewer with 20% of studies also independently appraised by a second reviewer. Meta-analyses will be conducted if sufficient homogeneity between studies permits. Otherwise, a narrative synthesis of results will be undertaken.

Ethics and dissemination

As this is a review of published literature, no ethics approval is required. Findings will be disseminated through a journal article publication, conference presentations and plain-text summaries for public accessibility.

PROSPERO registration number

CRD42024534813.
Machine-learning versus traditional methods for prediction of all-cause mortality after transcatheter aortic valve implantation: a systematic review and meta-analysis
Authors: Zaka Ammar , Mustafiz Cecil , Mutahar Daud , Sinhal Shreyans , Gorcilov James , Muston Benjamin , Evans Shaun , Gupta Aashray , Stretton Brandon , Kovoor Joshua , Mridha Naim , Sivagangabalan Gopal , Thiagalingam Aravinda , Ramponi Fabio , Chan Justin , Bennetts Jayme , Murdoch Dale J , Zaman Sarah , Chow Clara K , Jayasinghe Rohan , Kovoor Pramesh , Bacchi Stephen
Published: January 2025

Background

Accurate mortality prediction following transcatheter aortic valve implantation (TAVI) is essential for mitigating risk, shared decision-making and periprocedural planning. Surgical risk models have demonstrated modest discriminative value for patients undergoing TAVI and are typically poorly calibrated, with incremental improvements seen in TAVI-specific models. Machine learning (ML) models offer an alternative risk stratification that may offer improved predictive accuracy.

Methods

PubMed, EMBASE, Web of Science and Cochrane databases were searched until 16 December 2023 for studies comparing ML models with traditional statistical methods for event prediction after TAVI. The primary outcome was comparative discrimination measured by C-statistics with 95% CIs between ML models and traditional methods in estimating the risk of all-cause mortality at 30 days and 1 year.

Results

Nine studies were included (29 608 patients). The summary C-statistic of the top performing ML models was 0.79 (95% CI 0.71 to 0.86), compared with traditional methods 0.68 (95% CI 0.61 to 0.76). The difference in C-statistic between all ML models and traditional methods was 0.11 (p<0.00001). Of the nine studies, two studies provided externally validated models and three studies reported calibration. Prediction Model Risk of Bias Assessment Tool tool demonstrated high risk of bias for all studies.

Conclusion

ML models outperformed traditional risk scores in the discrimination of all-cause mortality following TAVI. While integration of ML algorithms into electronic healthcare systems may improve periprocedural risk stratification, immediate implementation in the clinical setting remains uncertain. Further research is required to overcome methodological and validation limitations.
Persistently different patterns of patient’s global assessment of health in rheumatoid arthritis are associated with pain and impaired function more than with inflammation: an inception cohort study over 15 years
Authors: Bala Valentina , Hafström Ingiäld , Svensson Björn , Ajeganova Sofia
Published: January 2025

Objective

To assess patient’s self-reported global assessment of health (PGA) in relation to inflammation, pain and disability in patients with rheumatoid arthritis (RA).

Methods

Data were obtained from the Better Anti-Rheumatic PharmacOTherapy early RA cohort, in which patients were scheduled for follow-up of 15 years. Longitudinal PGA trajectories were identified using hierarchical agglomerative clustering procedure with Wards methods, based on PGA assessments during the first 2 years. Multivariate linear regression and mixed models were used to evaluate associations between PGA, inflammation, pain and disability.

Results

Totally 2238 patients were included in 1991–2006. Three PGA trajectories were identified, low, medium and high, including 34%, 48% and 18% of the patients, respectively. The similar PGA patterns were shown for the inclusion periods before and after 1999. The patients in the low PGA group were less often women, had lower body mass index, lower levels of inflammatory variables, visual analogue scale (VAS) pain and Health Assessment Questionnaire (HAQ) scores at baseline than patients in the higher PGA groups. After adjustments, smoking and antibodies to cyclic citrullinated peptide status differentiated between being in low and high PGA groups. During the first year, all PGA groups showed improved outcomes, most pronounced in low PGA group. Fewer patients in high PGA group achieved remission, independent of remission criteria used. The outcomes were consistently different between the PGA groups from 6 months and onwards. The PGA levels from baseline over 15 years were best explained by VAS pain, followed by HAQ score, Disease Activity Score on 28 joints-3 and tender joint count, adjusted R2up to 77%, 41%, 27% and 26%, respectively.

Conclusion

Persistently higher PGA levels in RA were mostly related to pain and disability.
Switching to biological DMARDs versus cycling among JAK inhibitors in patients with rheumatoid arthritis and with inadequate response to JAK inhibitors: from FIRST registry
Authors: Miyazaki Yusuke , Nakayamada Shingo , Tanaka Hiroaki , Hanami Kentaro , Fukuyo Shunsuke , Kubo Satoshi , Yamaguchi Ayako , Miyagawa Ippei , Satoh-Kanda Yurie , Todoroki Yasuyuki , Inoue Yoshino , Ueno Masanobu , Tanaka Yoshiya
Published: January 2025

Objectives

This study aimed to identify characteristics of patients with rheumatoid arthritis (RA) with an inadequate response to Janus kinase inhibitors (JAKi-IR) and evaluate the efficacy and safety of subsequent treatments.

Methods

This study included 434 patients with RA who started JAKi treatment. JAKi-IR patients were those who switched to another drug due to inadequate response or did not reach low disease activity within 26 weeks of beginning JAKi. The efficacy and safety of switched biological disease-modifying anti-rheumatic drugs (bDMARDs) or cycled targeted synthetic disease-modifying anti-rheumatic drugs were analysed 26 weeks after switching treatment in JAKi-IR patients.

Results

Patients with JAKi-IR RA accounted for 31.8% (n=138/434). Multiple logistic regression identified factors contributing to JAKi-IR, such as the prior use of multiple ineffective bDMARDs and suboptimal JAKi dosing. There were no differences in patient background when comparing patients with RA with JAKi-IR who cycled to another JAKi (n=31) versus those who switched to bDMARDs (n=45). Among those cycling to another JAKi, the Clinical Disease Activity Index (CDAI) scores improved by week 26, with higher remission rates, while retention and adverse events remained similar. Trajectory analysis identified three CDAI response patterns, with the ‘treatment response’ group showing rapid and sustained improvement when cycling to another JAKi. Multiple logistic regression in this group identified another JAKi cycle as the critical factor for the treatment response.

Conclusions

Cycling JAKis is more effective than switching to bDMARDs in JAKi-IR RA, with no differences in safety or retention. This study suggests that cycling to another JAKi may be appropriate for patients with RA with JAKi-IR.
Massless limit and conformal soft limit for celestial massive amplitudes
Authors: Fan Wei
Published: January 2025

In celestial holography, the massive and massless scalars in 4d space-time are represented by the Fourier transform of the bulk-to-boundary propagators and the Mellin transform of plane waves respectively. Recently, the 3pt celestial amplitude of one massive scalar and two massless scalars was discussed in arXiv:2312.08597. In this paper, we compute the 3pt celestial amplitude of two massive scalars and one massless scalar. Then we take the massless limit

$$m\rightarrow 0$$

m
→
0

for one of the massive scalars, during which process the gamma function

$$\Gamma (1-\Delta )$$

Γ
(
1
-
Δ
)

appears. By requiring the resulting amplitude to be well-defined, that is it goes to the 3pt amplitude of arXiv:2312.08597, the scaling dimension of this massive scalar has to be conformally soft

$$\Delta \rightarrow 1$$

Δ
→
1

. The pole

$$1/(1-\Delta )$$

1
/
(
1
-
Δ
)

coming from

$$\Gamma (1-\Delta )$$

Γ
(
1
-
Δ
)

is crucial for this massless limit. Without it the resulting amplitude would be zero. This can be compared with the conformal soft limit in celestial gluon amplitudes, where a singularity

$$1/(\Delta -1)$$

1
/
(
Δ
-
1
)

arises and the leading contribution comes from the soft energy

$$\omega \rightarrow 0$$

ω
→
0

. The phase factors in the massless limit of massive conformal primary wave functions, discussed in arXiv:1705.01027, plays an import and consistent role in the celestial massive amplitudes. Furthermore, the subleading orders

$$m^{2n}$$

m

2
n

can also contribute poles when the scaling dimension is analytically continued to

$$\Delta =1-n$$

Δ
=
1
-
n

or

$$\Delta = 2$$

Δ
=
2

, and we find that this consistent massless limit only exists for dimensions belonging to the generalized conformal primary operators

$$\Delta \in 2-{\mathbb {Z}}_{\geqslant 0}$$

Δ
∈
2
-

Z

⩾
0

of massless bosons.
Defining quantum games
Authors: Piispanen Laura , Pfaffhauser Marcel , Wootton James , Togelius Julian , Kultima Annakaisa
Published: January 2025

In this research article, we survey existing quantum physics-related games and, based on this survey, propose a definition for the concept of quantum games. We define a quantum game as any type of rule-based game that either employs the principles of quantum physics or references quantum phenomena or the theory of quantum physics through any of three proposed dimensions: the perceivable dimension of quantum physics, the dimension of quantum technologies, and the dimension of scientific purposes, such as citizen science or education. We also discuss the concept of quantum computer games, which are games on quantum computers, as well as definitions for the concept of science games. Various games explore quantum physics and quantum computing through digital, analogue, and hybrid means, with various incentives driving their development. As interest in games as educational tools for supporting quantum literacy grows, understanding the diverse landscape of quantum games becomes increasingly important. We propose that the three dimensions of quantum games identified in this article be used for designing, analysing, and defining the phenomenon of quantum games.
Determination of the τ/ε-Ratio for Gas Diffusion Substrates and Microporous Layers in a Proton Exchange Membrane Fuel Cell
Authors: Berger Anne , Striednig Michael , Simon Christoph , Gasteiger Hubert A.
Published: January 2025

An understanding of the GDL properties is crucial for high-current-density operation of proton exchange membrane fuel cells (PEMFCs). The parameters porosity (

ε

) and tortuosity (

τ

) directly link the theoretical diffusivity in free space and the effective diffusivity in the structure. The

τ
/
ε

-ratio is therefore an important descriptor for the gas diffusion in a porous network. This study characterizes the

τ
/
ε

-ratio for gas diffusion layer substrate (GDL-S) materials from two suppliers (Toray, Freudenberg) and for one microporous layer (MPL) using limiting current measurements in an operating fuel cell. However, only the application of a new analysis method that considers the contribution from Knudsen diffusion allows for the

τ
/
ε

-determination of GDL-S materials which have carbon black added to the structure (e.g., Freudenberg GDL-S); this method can then also be used for the determination of the

τ
/
ε

-ratio of porous networks containing small pores like MPLs. Here, we assess the contribution of pressure-independent Knudsen diffusion to the overall diffusion and introduce a mixed diffusion coefficient, which includes both Knudsen and molecular diffusion. This analysis serves as a guideline to estimate the contribution of the respective diffusive processes for gas diffusion materials utilized in PEMFCs, where pore sizes resulting in different diffusion regimes are present.
A Multipotent PROX1+ Tumor Stem/Progenitor Cell Population Emerges During Intestinal Tumorigenesis and Mediates Radioresistance in Colorectal Cancer
Authors: Kallio Pauliina , Bessone Cinzia , Seyednasrollah Fatemeh , Brodkin Jefim , Lassila Marika , Högström Jenny , González-Loyola Alejandra , Petrova Tatiana V. , Haglund Caj , Alitalo Kari
Published: January 2025

Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells. Most PROX1-lineage traced tumor cells were stem/progenitor cells, which can supply cells to multiple intestinal tumor cell lineages, whereas most lineage-traced LGR5+ tumor cells were enterocytes, indicating that PROX1+ and LGR5+ tumor stem cells have distinct differentiation programs. Although the PROX1+ tumor cells proliferated slower than PROX1- cells, irradiation increased the proportion of PROX1+ cells in human CRC cell lines, patient-derived organoids, and tumor xenografts. Furthermore, transcripts related to DNA damage repair (DDR) were enriched in PROX1+ vs. PROX1- cells in adenomas and in CRC tumor cells from patients. Experiments with PROX1 silencing and overexpression indicated that PROX1 expression enhances CRC cell colony formation following irradiation. PROX1 interacted with DDR proteins, including components of non-homologous end-joining (NHEJ) and base excision repair, and inhibition of NHEJ repair led to a decreased proportion of PROX1+ cells following irradiation. In conclusion, PROX1+ cells are irradiation-resistant tumor stem/progenitor cells capable of self-renewal and differentiation. DDR inhibitors could represent a strategy to target the treatment-resistant PROX1+ tumor stem cells.
Comparison of Lean, Obese, and Weight Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T Cell Populations
Authors: Pierro Elysa W. , Cottam Matthew A. , An Hanbing , Lehmann Brian D. , Pietenpol Jennifer A. , Wellen Kathryn E. , Makowski Liza , Rathmell Jeffrey C. , Fingleton Barbara , Hasty Alyssa H.
Published: January 2025

Obesity is an established risk factor for breast cancer development and poor prognosis. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression, and TREM2, a transmembrane receptor expressed on macrophages in adipose tissue and tumors, is an emerging therapeutic target for cancer. A better understanding of the mechanisms for the obesity-breast cancer association and the potential benefits of weight loss could help inform treatment strategies. Here, we utilized lean, obese, and weight loss mouse models to examine the impacts of TREM2 deficiency (Trem2+/+ and Trem2-/-) on postmenopausal breast cancer depending on weight history conditions. Trem2 deficiency constrained tumor growth in lean, but not obese or weight loss, mice. Single-cell RNA sequencing, in conjunction with VDJ sequencing of tumor and tumor-adjacent mammary adipose tissue (mATTum-adj) immune cells, revealed differences in the immune landscapes across the different models. Tumors of lean Trem2-/- mice exhibited a shift in clonal CD8+ T cells from an exhausted to an effector memory state, accompanied increased clonality of CD4+ Th1 cells, that was not observed in any other diet-genotype group. Notably, identical T cell clonotypes were identified in the tumor and mATTum-adj of the same mouse. Finally, anti-PD-1 therapy restricted tumor growth in lean and weight loss, but not obese, mice. These findings indicate that weight history could impact the efficacy of TREM2 inhibition in postmenopausal breast cancer. The reported immunological interactions between tumors and the surrounding adipose tissue highlight significant differences under obese and weight loss conditions.
Beliefs About the Speaker’s Reasoning Ability Influence Pragmatic Interpretation: Children and Adults as Speakers
Authors: Mayn Alexandra , Loy Jia E. , Demberg Vera
Published: January 2025

The cooperative principle states that communicators expect each other to be cooperative and adhere to rational conversational principles. Do listeners keep track of the reasoning sophistication of the speaker and incorporate it into the inferences they derive? In two experiments, we asked participants to interpret ambiguous messages in the reference game paradigm, which they were told were sent either by another adult or by a 4-year-old child. We found an effect of speaker identity: if sent by an adult, an ambiguous message was much more likely to be interpreted as an implicature, while if sent by a child, it was a lot more likely to be interpreted literally. We also observed substantial individual variability, which points to different beliefs and strategies among our participants. We discuss how these speaker effects can be modeled in the Rational Speech Act framework.
“Groupitizing”: A Visuo-Spatial and Arithmetic Phenomenon
Authors: Maldonado Moscoso Paula A. , Anobile Giovanni , Maduli Giuseppe , Arrighi Roberto , Castaldi Elisa
Published: January 2025

When objects are grouped in space, humans can estimate numerosity more precisely than when they are randomly scattered. This phenomenon, called groupitizing, is thought to arise from the interplay of two components: the subitizing system which identifies both the number of subgroups and of items within each group, and the possibility to perform basic arithmetic operations on the subitized groups. Here we directly investigate the relative role of these two components in groupitizing via an interference (dual task) paradigm. Participants were required to estimate numerosities of grouped and ungrouped arrays while their attentional resources were fully available (single task) or while performing concurrent tasks loading auditory or visuo-spatial attention (both known to interfere with the subitizing process) as well as while performing arithmetic calculation. The attentional cost of performing any concurrent task was overall higher for grouped than ungrouped stimuli, supporting the idea that groupitizing relies on the recruitment of more than one attention-dependent mechanism. However, depriving visuo-spatial attention and preventing participants from performing calculations caused the strongest decrement in sensory precision for grouped numerosities indicating that these attentional components play a major role in groupitizing. These results are in line with the existence of an estimation mechanism that might operate across all numerical ranges, supplemented by attentional mechanisms (subitizing). This study shows that this attentional-demanding mechanism can be activated also when processing numerosities outside of the subitizing regime (n > 4), provided that grouping cues are available and, in concert with calculation abilities, gives rise to the groupitizing phenomenon.
On the Perception of Moral Standing to Blame
Authors: Ghezae Isaias , Yang Fan , Yu Hongbo
Published: January 2025

Is everyone equally justified in blaming another’s moral transgression? Across five studies (four pre-registered; total N = 1,316 American participants), we investigated the perception of moral standing to blame—the appropriateness and legitimacy for someone to blame a moral wrongdoing. We propose and provide evidence for a moral commitment hypothesis—a blamer is perceived to have low moral standing to blame a moral transgressor if the blamer demonstrates weak commitment to that moral rule. As hypothesized, we found that when blamers did not have the chance or relevant experience to demonstrate good commitment to a moral rule, participants generally believed that they had high moral standing to blame. However, when a blamer demonstrated bad commitment to a moral rule in their past behaviors, participants consistently granted the blamer low moral standing to blame. Low moral standing to blame was generally associated with perceiving the blame to be less effective and less likely to be accepted. Moreover, indirectly demonstrating moral commitment, such as acknowledging one’s past wrongdoing and feeling/expressing guilt, modestly restored moral standing to blame. Our studies demonstrate moral commitment as a key mechanism for determining moral standing to blame and emphasize the importance of considering a blamer’s moral standing as a crucial factor in fully understanding the psychology of blame.
Dictyanthus reflexiflorus (Apocynaceae: Asclepiadoideae) a new species from Mexico
Authors: LOZADA-PÉREZ LUCIO , CORTEZ ERICKA B. , PEREZ-GARCIA MARIA DE LA LUZ , GONZÁLEZ CÉSAR RAMIRO MARTÍNEZ , MARTÍNEZ-AMBRIZ EMMANUEL
Published: January 2025

A new species of Dictyanthus from the state of Michoacan, Mexico, is described and illustrated Dictyanthus reflexiflorus sp. nov. It grows in tropical deciduous forests located in the municipality of Tacámbaro. A phylogenetic analysis based on molecular data (plastid regions trnL-trnF and rps 16) was conducted to explore the relationship of the new species. Results place the new species in Dictyanthus. The morphological characters that support this relationship are the presence of uncinate hairs and a reticulate corolla. The species has unique characteristics within the genus, such as a reflexed corolla and the tube 10-lobed closely pressed to the side of the gynostegium. A key to distinguish Dictyanthus reflexiflorus from congeners in Mexico is included.
Ceropegia antoanensis (Apocynaceae: Ceropegieae), a new species from Vietnam
Authors: NGUYEN-LE XUAN BACH , NGUYEN HIEU CUONG , TRAN THE BACH , LUU HONG TRUONG
Published: January 2025

Ceropegia antoanensis is described and illustrated as a new species endemic to Central Vietnam. The new taxon is morphologically allied to C. ansariana but differs in a number of characteristics. The phenology, distribution and provisional IUCN assessment of conservation status of the new taxon are provided.
A new species of Ferulago (Apiaceae) from Türkiye
Authors: HAMZAOĞLU ERGİN
Published: January 2025

Some interesting Ferulago (Apiaceae) specimens with long stems, 7–9 mm long bracts, and 8–11 mm wide mericarps were collected from Horasan District (Erzurum Province, Türkiye). At first glance, the specimens resembled the species Ferulago setifolia (sect. Eutaenia) as a habit. However,  through a detailed examination, it was determined that there were some differences. Based on these differences, the specimens are presented to the scientific world as a new species named “Ferulago turcica”. The most obvious attributes that separate the new species from Ferulago setifolia, that is the closest taxon, are: blades of basal leaves triangular in outline and 3-pinnatisect (not linear-lanceolate and (3-)4-pinnatisect); terminal lobes of basal leaves 1–3 mm long and apiculate at apex (not 5–8(–12) mm long and setaceous-filiform at apex); bracts oblong and 7–9 mm long (not linear-lanceolate and 7–17 mm long); pedicels 9–14 and 3–6 mm long (not 8–10 and 7–11 mm long); mericarps 9–11 mm wide and broadly obovate-elliptic (not 7–8 mm wide and oblong-elliptic); epicuticular wax on the mericarp body sparsely irregular (not dense irregular). This study provided an elucidation outlining the attributes of the newly discovered species, complemented by photographic evidence and an overview of its broader ecological inclinations.
Two new species with tiny flowers for the genus Racinaea (Bromeliaceae)
Authors: GOUDA ERIC J.
Published: January 2025

Two new species of Racinaea are described and illustrated. Diagnoses against their most morphologically similar taxa and illustrations are provided. One of the new taxa is only known from Colombia and the other one from Peru.
An integrative taxonomic assessment leads to the synonymy of the Waccamaw Crayfish Procambarus braswelli Cooper 1998 with the Cedar Creek Crayfish Procambarus chacei Hobbs 1958 (Decapoda: Cambaridae)
Authors: KENDRICK MICHAEL R. , WILLIAMS BRONWYN W.
Published: January 2025

The southeastern United States (U.S.) is a global hotspot for crayfish diversity, with the majority of the >350 species known in the U.S. occurring here. Crayfishes in the genus Procambarus are common in lower gradient lotic and lentic systems of the southeast, but from both a taxonomic and systematic perspective, this genus is largely neglected in comparison to other crayfish genera. The aim of this study is to clarify the taxonomic status of two conservation priority crayfishes from the southeastern U.S. by testing the hypothesis that Procambarus braswelli Cooper, 1998 and Procambarus chacei Hobbs, 1958 are distinct species. We conducted a geometric morphometric analysis of these species, including 16 morphological metrics across 51 specimens throughout the ranges of these species in North Carolina and South Carolina. We then isolated, extracted, and sequenced a fragment of the COI gene and used maximum likelihood phylogenetic analysis to determine genetic distinctness. Results of multivariate analyses show overlapping morphologies between species and genetic structure that does not co-vary with original species determinations. Together, the available morphological and genetic information indicates that P. chacei and P. braswelli be synonymized. Additional taxonomic, life history, and ecological work is sorely needed for Procambarus crayfishes of the species-rich southeastern U.S.
A new genus of hybotid dance fly (Diptera: Hybotidae, Tachydromiinae) from the Eocene Sakhalinian amber
Authors: SHAMSHEV IGOR V. , VASILENKO DMITRY V. , PERKOVSKY EVGENY E.
Published: January 2025

The family Hybotidae (Insecta: Diptera, Empidoidea) is recorded for the first time from the bio-inclusions of Sakhalinian amber (Russia). Almost all inclusions studied belong to the subfamily Tachydromiinae. First results suggest that tachydromiines were not uncommon in a palaeo-biotope, where a resin known nowadays as Sakhalinian amber was produced. A new genus and species, Eoplatypalpus sachalinensis gen. et sp. nov., are described and illustrated. In addition, the inclusions of two tachydromiine species of unclear genera (or genus) have been examined but not named. Preliminarily, the palaeo-fauna of Tachydromiinae of Sakhalinian amber is characterised by the presence of only primitive representatives. They show an affinity with the most primitive extant genera of the subfamily (such as Symballophthalmus Becker and Megagrapha Melander) and with the group of extinct genera known from Upper Cretaceous inclusions (Cretoplatypalpus group of genera). The paleontological records of Tachydromiinae are briefly discussed. In addition, it is shown that Symballophthalmus clavilabrosus Hong described from Ypresian Fushun amber of China actually belongs to a different, as of yet uncertain genus. Consequently, fossils of the primitive extant genus Symballophthalmus remain unknown. An identification key to fossil genera of Tachydromiinae (exclusive of Drapetidini) is provided.
Two new species of Apateticinae from Guangxi, China (Coleoptera: Staphylinidae)
Authors: CHANG JIN-KANG , SCHILLHAMMER HARALD , TANG LIANG
Published: January 2025

Two new species of Apateticinae from Guangxi, southern China are described: Apatetica xuyuhaoi Chang, Schillhammer & Tang, sp. nov. and Nodynus huapingensis Chang, Schillhammer & Tang, sp. nov. These species are characterized, and compared to similar congeners, supplemented with illustrations of the habitus and sexual characters.
First record of “Bigeye trevally” Caranx sexfasciatus Quoy & Gaimard 1825 (Carangiformes: Carangidae) from Peru
Authors: CAMPOS-LEÓN SARITA , MIRANDA-ROMERO JUNIOR , MORENO ANDREY , RAMÍREZ JORGE L. , SICCHA-RAMIREZ ZOILA RAQUEL
Published: January 2025

Specimens of Caranx sexfasciatus (Bigeye trevally) were collected from northern and central Peru between 2021 and 2023, marking the first confirmed record of this species in Peruvian waters. This study represents a significant extension of its known range, previously reported only as far south as Ecuador. Morphological and molecular analyses were conducted to confirm species identification, revealing diagnostic coloration and physical traits. Observations near oil platforms suggest artificial reefs play a critical role in its habitat preference. The species’ presence in the Humboldt Current may be linked to the El Niño-Southern Oscillation (ENSO), which elevates sea temperatures and influences marine biodiversity distribution. This report not only extends the known range of C. sexfasciatus but also highlights the ecological importance of artificial reefs and climate events in shaping its distribution.
GATA2 links stemness to chemotherapy resistance in acute myeloid leukemia.
Authors: Alikarami Fatemeh , Xie Hongbo M , Riedel Simone S , Goodrow Haley , Barrett Declan Raymond , Mahdavi Leila , Lenard Alexandra , Chen Changya , Yamauchi Taylor , Danis Etienne , Cao Zhendong , Tran Vu Le-Huy , Jung Mabel Minji , Li Yapeng , Huang Hua , Shi Junwei , Tan Kai , Teachey David Trent , Bresnick Emery H , Neff Tobias , Bernt Kathrin Maria
Published: January 2025

Stemness-associated cell states are linked to chemotherapy resistance in AML. We uncovered a direct mechanistic link between expression of the stem cell transcription factor GATA2 and drug resistance. The GATA-binding protein 2 (GATA2) plays a central role in blood stem cell generation and maintenance. We find substantial intra- and inter-patient variability in GATA2 expression across AML patient samples. GATA2 expression varies by molecular subtype and has been linked to outcome. In a murine model, KMT2A-MLL3 driven AML originating from a stem cell or immature progenitor cell population have higher Gata2 expression and are more resistant to the standard AML chemotherapy agent doxorubicin. Deletion of Gata2 resulted in more robust induction of p53 following exposure to doxorubicin. ChIP-Seq, RNA-Seq and functional studies revealed that GATA2 regulates the expression of RASSF4, a modulator of the p53 inhibitor MDM2. GATA2 and RASSF4 are anti-correlated in human cell lines and AML patient cell bulk and single cell expression datasets. Knockdown of Rassf4 in Gata2 low cells resulted in doxorubicin or nutlin-3 resistance. Conversely, overexpression of Rassf4 results in sensitization of cells expressing high levels of Gata2. Finally, doxorubicin and nutlin-3 are synergistic in Gata2-high murine AML, as well as AML patient samples. We discovered a previously unappreciated role for GATA2 in dampening p53-mediated apoptosis via transcriptional regulation of RASSF4, a modulator of MDM2. This role for GATA2 directly links the expression of a stemness associated transcription factor to chemotherapy resistance.
Analysis methods for covariate-constrained cluster randomized trials with time-to-event outcomes
Authors: Crisp Amy M. , Halloran M. Elizabeth , Hitchings Matt D. T. , Longini Ira M. , Dean Natalie E.
Published: January 2025

Background

Cluster randomized trials, which often enroll a small number of clusters, can benefit from constrained randomization, selecting a final randomization scheme from a set of known, balanced randomizations. Previous literature has addressed the suitability of adjusting the analysis for the covariates that were balanced in the design phase when the outcome is continuous or binary. Here we extended this work to time-to-event outcomes by comparing two model-based tests and a newly derived permutation test. A current cluster randomized trial of vector control for the prevention of mosquito-borne disease in children in Mexico is used as a motivating example.

Methods

We assessed type I error rates and power between simple randomization and constrained randomization using both prognostic and non-prognostic covariates via a simulation study. We compared the performance of a semi-parametric Cox proportional hazards model with robust variance, a mixed effects Cox model, and a permutation test utilizing deviance residuals.

Results

The permutation test generally maintained nominal type I error—with the exception of the unadjusted analysis for constrained randomization—and also provided power comparable to the two Cox model-based tests. The model-based tests had inflated type I error when there were very few clusters per trial arm. All three methods performed well when there were 25 clusters per trial arm, as in the case of the motivating example.

Conclusion

For time-to-event outcomes, covariate-constrained randomization was shown to improve power relative to simple randomization. The permutation test developed here was more robust to inflation of type I error compared to model-based tests. Gaining power by adjusting for covariates in the analysis phase was largely dependent on the number of clusters per trial arm.
Safety and efficacy of intravenous thrombolysis: a systematic review and meta-analysis of 93,057 minor stroke patients
Authors: Moawad Mostafa Hossam El Din , Salem Talal , Alaaeldin Anas , Elaraby Youssef , Awad Peter D. , Khalifa Amr Ahmed , Naggar Ahmed El , Mohamed Khaled Ashraf , Elhalal Mohamed , Badr Mostafa , Abdelnaby Ramy
Published: January 2025

Background

The definition of minor ischemic stroke (MIS) is a topic of debate, however, the most accepted definition is a stroke with National Institutes of Health Stroke Scale (NIHSS) ≤ 5. Intravenous thrombolysis (IVT) is a crucial treatment option for acute ischemic stroke (AIS) including: alteplase, recombinant human tissue-type plasminogen activator (r-tPA), and the recently approved tenecteplase. However, there is a debate regarding its safety and efficacy. Therefore, our objective was to determine the safety and efficacy of IVT in treating minor stroke patients (NIHSS ≤ 5).

Methods

Using the search strategy assigned which was based on three keywords: “mild” or “minor”, “stroke”, and “intravenous thrombolysis”, we searched for eligible articles on PubMed, Web of Science, Embase, and Scopus from inception till 10th January 2024. We conducted this meta-analysis using the random effect model to account for the heterogeneity among the studies. For the dichotomous variables, we calculated the odds ratio (OR) from the event and total of these variables. While for the continuous variables, we calculated the mean difference (MD) of these variables. Pooling of OR for the occurrence of events was also conducted.

Results

A total of 21 articles with 93,057 patients with MIS were included. The mean age of the participants ranged from 62.3 to 79.6. Most of the included patients had comorbidities such as hypertension, diabetes, previous stroke, smoking, atrial fibrillation, and hyperlipidemia. Of these, 10,850 received IVT while 82,207 did not. The use of IVT was statistically significant associated with 90-day modified Rankin score (mRs) 0–1 when compared with control with OR of 1.67 (95%CI: 1.46, 1.91, p < 0.00001) and was statistically significantly associated with improvement of NIHSS on discharge with OR of 2.19 (95%CI: 1.56, 3.08, p < 0.00001). In terms of safety outcomes, IVT has proven a safe profile, as there was no significant difference in intracranial hemorrhage (ICH) and mortality rates between the IVT and control groups with OR of 1.75 (95CI: 0.95, 3.23, p = 0.07) and 0.93 (95%CI: 0.77, 1.11, p = 0.41), respectively.

Conclusion

Although some studies have not found any benefits of IVT in MIS patients, a substantial body of literature strongly endorses IVT as an effective and safe treatment for MIS. IVT has been shown to improve the mRs and NIHSS scores at the 90-day mark without an increased risk of ICH or mortality.
Positive real-time PCR in pneumococcal meningitis 12 hours after initiation of antibiotic therapy – case report
Authors: Thunstedt Cem , Palleis Carla , Wischmann Johannes , Heck Suzette , Dimitriadis Konstantinos , Klein Matthias
Published: January 2025

Background

Purulent meningitis poses a significant clinical challenge with high mortality. We present the case of a 54-year-old female transferred to our emergency department with suspected bacterial meningitis, later diagnosed as an Austrian syndrome.

Case presentation

The patient exhibited subacute somnolence, severe headache, nausea and fever. Initial antibiotic therapy was initiated without successful lumbar puncture. Upon arrival at our hospital, she presented with septic shock, meningism, and respiratory symptoms. Lumbar puncture revealed cloudy cerebrospinal fluid with elevated cell count, protein, and low glucose. While blood and CSF cultures remained negative, multiplex PCR for Streptococcus pneumoniae was positive even 10 h after beginning of effective antibiotic therapy. Subsequent echocardiogram revealed mitral valve endocarditis and the patient underwent valve replacement.

Conclusion

Altogether, bacterial meningitis presents with cardinal clinical signs only half of cases. Lumbar puncture remains crucial, and our patient’s CSF findings aligned with bacterial meningitis. Multiplex PCR aided in diagnosis, even after antibiotic treatment. The case highlights the importance of prompt lumbar puncture despite antibiotic pre-treatment. The patient’s Austrian syndrome, characterized by meningitis, endocarditis, and pneumonia, emphasizes the need for vigilance regarding skin lesions, early cerebral infarctions, and iritis. This case emphasizes the complexity of bacterial meningitis diagnosis and the utility of multiplex PCR, especially in prolonged antibiotic-treated patients. However, PCR cannot replace cultures when it comes to adapting therapy based on the antibiotic sensitivity of the causative pathogen. Awareness of Austrian syndrome’s diverse manifestations is crucial for timely recognition and appropriate management.
Time to first antenatal care visit and its predictors among women in Kenya: Weibull gamma shared frailty model (based on the recent 2022 KDHS data)
Authors: Kase Bizunesh Fantahun , Seifu Beminate Lemma , Mare Kusse Urmale , Shibeshi Abdu Hailu , Asebe Hiwot Altaye , Gemeda Kebede , Asmare Zufan Alamrie , Asgedom Yordanos Sisay , Fente Bezawit Melak , Lombebo Afework Alemu , Tebeje Tsion Mulat
Published: January 2025

Background

The first trimester of pregnancy is critical for fetal development, making early antenatal care visits essential for timely check-ups and managing potential complications. However, delayed antenatal care initiation remains a public health challenge in sub-Saharan Africa, including Kenya. Therefore, this study aimed to assess and provide up-to-date information on time to first antenatal care visit and its predictors among women in Kenya, using data from the most recent 2022 Kenya Demographic and Health Survey (KDHS).

Methods

This community-based cross-sectional study analyzed data from 19,530 birth histories in the 2022 Kenya Demographic and Health Survey (KDHS). The primary outcome was the timing of the first antenatal care (ANC) visit, classified as timely if it occurred in the first trimester. Shared frailty survival models were used to account for the hierarchical data structure and unobserved heterogeneity, with the Weibull gamma model identified as the best fit based on Information Criteria (AIC), and Bayesian Information Criteria (BIC). Variables with p < 0.2 entered multivariable analysis, and results were reported as Adjusted Hazard Ratios (AHR) with 95% Confidence Intervals (CI) using the Weibull gamma model.

Results

The study found that the median time for the first antenatal care (ANC) visit in Kenya was four months. Significant predictors of ANC timing included women’s age (35–49 years: AHR 0.83; 95% CI: 0.72–0.95), education level (higher: AHR 1.45; 95% CI: 1.17–1.78), media exposure (yes: AHR 1.21; 95% CI: 1.05–1.39), parity (four or more children: AHR 0.81; 95% CI: 0.72–0.91), wealth status (richest: AHR 2.00; 95% CI: 1.63–2.43), desire for more children (did not want more: AHR 0.64; 95% CI: 0.54–0.77), residence (rural: AHR 1.22; 95% CI: 1.07–1.39), and religion (Islam: AHR 0.76; 95% CI: 0.64–0.89).

Conclusion

The median time for the first ANC visit exceeds the World Health Organization’s recommendation of initiating care within the first trimester. These findings underscore the need for targeted interventions to promote timely ANC, especially among women with limited media exposure, high parity, lower socioeconomic status, and specific religious followers.
Atherogenic index of plasma and coronary artery disease: a systematic review and meta-analysis of observational studies
Authors: Assempoor Ramin , Daneshvar Mohammad Shahabaddin , Taghvaei Aryan , Abroy Alireza Sattari , Azimi Amir , Nelson John R. , Hosseini Kaveh
Published: January 2025

Background

Atherogenic index of plasma (AIP), a novel logarithmic index that combines fasting triglyceride and high-density lipoprotein cholesterol concentrations, is associated with the burden of atherosclerosis. This study aimed to evaluate the relationship between AIP and coronary artery disease (CAD) risk, severity, and prognosis in populations with and without established CAD.

Methods

PubMed, Embase, and Web of Science were systematically searched from the inception of each database to August 13, 2024. Cross-sectional studies, case-control studies, and prospective or retrospective cohort studies using multivariate analysis were included. Given that the true effect size may differ across studies, a random-effects model for all analyses was applied.

Results

Fifty-one observational studies were included in this study. Patients with higher AIP were more likely to have CAD (odds ratio (OR): 2.79, 95% CI 1.75–4.45, P < 0.00001). Furthermore, these patients were more likely to have coronary artery calcification (OR: 2.28, 95% CI 1.74–3.00, P < 0.00001), multivessel CAD (OR: 2.04, 95% CI 1.50–2.77, P < 0.00001), and an increased risk of plaque progression (OR: 1.49, 95% CI 1.17–1.91, P = 0.001). In populations without established CAD, higher AIP levels were associated with an increased risk of Major adverse cardiovascular events (MACE) (hazard ratio (HR): 1.28, 95% CI 1.22–1.35, P < 0.00001). Interestingly, this finding was consistent in patients presenting with acute coronary syndrome (HR: 1.59, 95% CI 1.33–1.89, P < 0.00001) and patients with chronic coronary syndrome or stable CAD (HR: 1.65, 95% CI 1.15–2.37, P = 0.007).

Conclusions

This meta-analysis demonstrates that elevated AIP is strongly associated with increased CAD risk, greater severity, and poorer prognosis in populations with and without established CAD. However, more studies are needed to evaluate the predictive performance and determine the optimal cut-off for AIP in different populations.

Graphical abstract