bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Medically Resistant Intramuscular Fast-Flow Vascular Anomaly in a Young Adult Patient Managed With Embolization and Cryoablation
Authors: Patel Kristy , Schoeman Sean , Cahill Anne Marie
Published: April 2024

Background:

Mitogen-activated protein 2 kinase (MAP2K) intramuscular high-flow vascular anomaly is a benign vascular lesion, thought to be congenital, with an indolent course. Years after initial presentation, symptoms may manifest due to abrupt growth.

Case presentation:

This report describes a case of a young female who presented with a MAP2K high-flow vascular anomaly with recalcitrant pain, resistant to a trial of Sirolimus and Trametinib. Significant lesion size reduction and pain resolution were achieved with a combination of preablation embolization followed by cryoablation. Follow-up of 5 years informs lesion reduction and stability.

Conclusion:

Using a multi-method approach (embolization then ablation) can be considered in the treatment of MAP2K high-flow vascular malformations resistant to medical therapy.
The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study
Authors: Wen Haoxiang , Huang Yihao , Huang Shaoqing , Xiao Han , Xie Wenxuan , Zhou Qian , Tan Li , Ding Yuqi , Liu Xiaofei , Yu Yang , Song Zimin , Shen Shunli , Chen Zebin , Zhang Xinhua
Published: April 2024

Background:

The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases.

Methods:

Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS.

Results:

Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P=0.015), and the liver-specific PFS (P=0.642) and PFS (P=0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P<0.001) and IM+HR (HR 0.361, P=0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P=0.034), liver-specific PFS (HR 0.388, P=0.014), and PFS (HR 0.402, P=0.004).

Conclusions:

In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.
In Patients With Inflammatory Bowel Disease, Racial Disparities Exist in Burden of Vaccine-preventable Disease Hospitalizations and Outcomes
Authors: Karime Christian , Salazar Miguel , Black Cecily N. , Caldera Freddy , Okafor Philip N. , Hammami Muhammad B. , Hashash Jana G. , Farraye Francis A.
Published: April 2024

Objective:

Patients with inflammatory bowel disease (IBD) are at increased risk of vaccine-preventable diseases (VPDs). Despite the increasing prevalence of IBD in non-white populations, little is known regarding racial disparities in VPD burden.

Methods:

Retrospectively analyzing the 2016 to 2020 National Inpatient Sample, we identified adults with IBD hospitalized for a principal diagnosis of VPD. The primary outcome investigated was hospitalization for VPD stratified by patient-reported race. Secondary outcomes were in-hospital morbidity, mortality, length of stay, and health care utilization. Multivariable regression analysis was performed to adjust for patient and hospital characteristics.

Results:

The search identified 554,114 hospitalizations for VPD, including 4170 hospitalizations in patients with IBD. Patients with IBD had significantly greater odds of hospitalization from herpes zoster virus (adjusted odds ratio [aOR]: 1.73) and varicella zoster virus (aOR: 2.31). Comparing white and non-white patients with IBD, significant racial disparities were noted. Non-white patients were at greater odds of hospitalization from influenza (aOR: 1.74), herpes zoster virus (aOR: 1.77), and varicella zoster virus (aOR: 1.62). In-hospital morbidity was greater in non-white patients, including greater odds of requiring intensive care unit stay (aOR: 1.18). Morbidity was elevated in African Americans, with greater odds of acute kidney injury (aOR: 1.25), venous thromboembolism (aOR: 1.17), respiratory failure (aOR: 1.16), and intensive care unit stay (aOR: 1.18). No differences were found in mortality, length of stay, and health care utilization.

Conclusions:

Significant racial disparities in VPD hospitalization and in-hospital morbidity were found among adults with IBD in the United States. With the increasing prevalence of IBD in non-white populations, targeted efforts are needed to improve health equity.
Association Between Medicare’s Sepsis Reporting Policy (SEP-1) and the Documentation of a Sepsis Diagnosis in the Clinical Record
Authors: Barbash Ian J. , Davis Billie S. , Saul Melissa , Hwa Rebecca , Brant Emily B. , Seymour Christopher W. , Kahn Jeremy M.
Published: April 2024

Study Design:

Interrupted time series analysis of a retrospective, electronic health record cohort.

Objective:

To determine the association between the implementation of Medicare’s sepsis reporting measure (SEP-1) and sepsis diagnosis rates as assessed in clinical documentation.

Background:

The role of health policy in the effort to improve sepsis diagnosis remains unclear.

Patients and Methods:

Adult patients hospitalized with suspected infection and organ dysfunction within 6 hours of presentation to the emergency department, admitted to one of 11 hospitals in a multi-hospital health system from January 2013 to December 2017. Clinician-diagnosed sepsis, as reflected by the inclusion of the terms “sepsis” or “septic” in the text of clinical notes in the first two calendar days following presentation.

Results:

Among 44,074 adult patients with sepsis admitted to 11 hospitals over 5 years, the proportion with sepsis documentation was 32.2% just before the implementation of SEP-1 in the third quarter of 2015 and increased to 37.3% by the fourth quarter of 2017. Of the 9 post-SEP-1 quarters, 8 had odds ratios for a sepsis diagnosis >1 (overall range: 0.98–1.26; P value for a joint test of statistical significance = 0.005). The effects were clinically modest, with a maximum effect of an absolute increase of 4.2% (95% CI: 0.9–7.8) at the end of the study period. The effect was greater in patients who did not require vasopressors compared with patients who required vasopressors (P value for test of interaction = 0.02).

Conclusions:

SEP-1 implementation was associated with modest increases in sepsis diagnosis rates, primarily among patients who did not require vasoactive medications.
Factor Xa inhibitors vs. warfarin in patients with Hughes syndrome: a systematic review and meta-analysis of randomized controlled trials
Authors: Mohtashim Ali , Azhar Aima , Mazhar Saad , Devi Deepa , Danial Muhammad , Patel Dhruvilkumar , Khan Owais , Andani Anushka , Khan Muhammad Mohib , Samad Shahzaib , Qureshi Aena , Ali Hafsa , Ejaz Umer , Jawad Sayed
Published: April 2024

Background:

The optimal treatment regimen for patients with Hughes syndrome remains unclear. Therefore, the authors sought to compare the outcomes of warfarin vs. factor Xa inhibitors in patients with Hughes syndrome.

Methods:

MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) comparing 8 efficacy and safety of warfarin and factor Xa inhibitors in patients with Hughes syndrome. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among 10 outcomes of interest. Mantel–Haenszel weighted random-effects model was used to calculate 11 relative risks (RRs) with 95% CIs.

Results:

The analysis included 625 patients from four RCTs and one post-hoc analysis. Meta-analysis showed a statistically non-significant difference between factor Xa inhibitors and warfarin in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); P=0.11, I2=50%]. Consistent results were revealed among patients with a previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); P=0.75, I2=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); P=0.31, I2=15%] and patients who were triple antiphospholipid antibodies (aPL) positive [RR 4.12 (95% CI 0.46, 37.10); 21 P=0.21, I2=58%]. Factor Xa inhibitors were significantly associated with an increased risk of stroke [RR 8.51 (95% CI 2.35, 13.82); P=0.47, I2=0%].

Conclusion:

Factor Xa inhibitors exhibited an increased risk of stroke among patients with Hughes syndrome. In addition, although not significant, the higher RRs among patients on factor Xa inhibitors may indicate a higher risk of thrombotic events associated with factor Xa inhibitors.
Effects of Cutting Planes on Costal Cartilage Warping
Authors: Ratanapoompinyo Sanathorn , Kiranantawat Kidakorn
Published: April 2024

Background:

Autogenous costal cartilage becomes a favorable choice for nasal reconstruction and complicated aesthetic rhinoplasty, because of its ample supply, sufficient for most patients. However, a notable drawback is the potential for warping. The authors’ study aims to identify cutting planes that minimize warping.

Methods:

Two hundred seven costal cartilage grafts were obtained by slicing the extracted costal cartilages from 10 fresh cadavers along 3 main planes: cephalocaudal, anteroposterior, and parallel to the synchondrosis plane. Each of these major planes was further divided into grafts taken from both the central and peripheral portions. Furthermore, both subgroups were categorized into three thicknesses: 1, 2, and 3 mm. The warping angles of all grafts were then compared at various time intervals after the initial cutting.

Results:

Cephalocaudal cuts exhibited significantly greater warping than other planes. Anteroposterior cuts displayed the least warping, although this difference lacked statistical significance. Peak warping occurred at 30 minutes. Certain grafts continued to warp even at 1 month. Central grafts had less warping than peripheral ones, although the difference was not statistically significant.

Conclusions:

Cephalocaudal cuts yielded the highest warping angle. Surgeons seeking thin (<3 mm) straight grafts should opt for anteroposterior or parallel to synchondrosis planes. Thicker grafts (>3 mm) can be cut in the cephalocaudal plane with an acceptable warping angle, close to parallel with the synchondrosis plane. For curved cartilage, thin cephalocaudal cutting is recommended. In addition, the authors suggest placing the cartilage in normal saline for at least 30 minutes, allowing for maximum warping to occur.
Incidental Finding of Spindle Cell Sarcoma on 68Ga-PSMA-11 PET/CT
Authors: Anigati Elena M. , Nguyen Nghi C.
Published: April 2024

A 78-year-old man underwent 68Ga–prostate-specific membrane antigen-11 (PSMA-11) PET/CT for biochemical recurrence of prostate adenocarcinoma following a simple prostatectomy. The scan showed PSMA-avid local recurrence within the prostatectomy bed and a suspicious right internal iliac nodal metastasis. In addition, there was a mildly avid subcutaneous lesion in the right flank, which revealed high-grade spindle cell sarcoma at histopathology. This case represents a potential pitfall for PSMA-11 PET imaging. The presentation of mildly avid, atypical soft tissue lesions should warrant a biopsy to allow for proper diagnosis and treatment management.
Isolation of Bioactive Compounds from Low-cost Agricultural Resources and its Utilization in Daily Life.
Authors: Debnath Anirban , Das Arpita
Published: April 2024

The ethanolic (80%), methanolic (80%) and aqueous decoction (100% distilled water) of whole plant of Oxalis corniculata Linn (Indian Sorrel) was evaluated for its anti‐microbial and antioxidant properties by in vitro methods.  Methanolic (80%) and ethanolic (80%) decoctions showed significant antibacterial property against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Salmonella typhi bacterial strains. In comparison to Chloramphenicol (C30) against bacteria, 80% ethanolic decoctions showed significant effect, among the decoctions. Nowadays though the standard soap is in a huge demand but it’s also facing major backlashes due to the presence of synthetic compounds in it, which over long use may cause harmful effects on the skin health. Therefore, the organic soaps which are made up of natural ingredients, herbs or any sort ayurvedic compound have less side effects on the human skin and are much safer than standard daily soap. The formulated therapeutic soap exhibits significant amount of reducing potential (high FRAP and TAC values) and antioxidant activity (DPPH, ABTS assay).
Refining the taxonomy of the order Hyphomicrobiales (Rhizobiales) based on whole genome comparisons of over 130 type strains
Authors: diCenzo George C. , Yang Yuqi , Young J. Peter W. , Kuzmanović Nemanja
Published: April 2024

The alphaproteobacterial order Hyphomicrobiales consists of 38 families comprising at least 152 validly published genera as of January 2024. The order Hyphomicrobiales was first described in 1957 and underwent important revisions in 2020. However, we show that several inconsistencies in the taxonomy of this order remain and we argue that there is a need for a consistent framework for defining families within the order. We propose a common genome-based framework for defining families within the order Hyphomicrobiales, suggesting that families represent monophyletic groups in core-genome phylogenies that share pairwise average amino acid identity values above ~75 % when calculated from a core set of 59 proteins. Applying this framework, we propose the formation of four new families and to reassign the genera Salaquimonas, Rhodoblastus, and Rhodoligotrophos into Salaquimonadaceae fam. nov., Rhodoblastaceae fam. nov., and Rhodoligotrophaceae fam. nov., respectively, and the genera Albibacter, Chenggangzhangella, Hansschlegelia, and Methylopila into Methylopilaceae fam. nov. We further propose to unify the families Bartonellaceae, Brucellaceae, Phyllobacteriaceae, and Notoacmeibacteraceae as Bartonellaceae; the families Segnochrobactraceae and Pseudoxanthobacteraceae as Segnochrobactraceae; the families Lichenihabitantaceae and Lichenibacteriaceae as Lichenihabitantaceae; and the families Breoghaniaceae and Stappiaceae as Stappiaceae. Lastly, we propose to reassign several genera to existing families. Specifically, we propose to reassign the genus Pseudohoeflea to the family Rhizobiaceae; the genera Oricola, Roseitalea, and Oceaniradius to the family Ahrensiaceae; the genus Limoniibacter to the emended family Bartonellaceae; the genus Faunimonas to the family Afifellaceae; and the genus Pseudochelatococcus to the family Chelatococcaceae. Our data also support the recent proposal to reassign the genus Prosthecomicrobium to the family Kaistiaceae.
Chelativorans salis sp. nov., a slightly halophilic bacterium isolated from an enrichment system with saline lake sediment
Authors: Gao Lei , She Ting-Ting , Liu Yong-Hong , Chen Zhong-Yan , Liu Jia-Yi , Jiang Hong-Chen , Fang Bao-Zhu , Li Wen-Jun
Published: April 2024

A Gram-stain-negative, non-motile, and slightly halophilic alphaproteobacterium, designated strain EGI FJ00035T, was isolated from enrichment sediment samples of a saline lake in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using the polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain EGI FJ00035T formed a distinct clade with ‘Chelativorans alearense’ UJN715 and ‘Chelativorans xinjiangense’ lm93 with sequence similarities of 98.44 and 98.22 %, respectively, while sharing less than 96.7 % with other valid type strains. The novel isolate could be distinguished from other species of the genus Chelativorans by its distinct phenotypic, physiological, and genotypic characteristics. Optimal growth of strain EGI FJ00035T occurred on marine agar 2216 at pH 7.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>5 %) were C19 : 0 cyclo ω8c, summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c), C16 : 0, C18 : 0, and iso-C17 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipids, unidentified glycolipids, and an unidentified lipid. Based on its genome sequence, the G+C content of strain EGI FJ00035T was 63.2 mol%. The average nucleotide identity, average amino acid identity, and digital DNA–DNA hybridization values of strain EGI FJ00035T against related members of the genus Chelativorans were below the thresholds for delineation of a novel species. According our polyphasic taxonomic data, strain EGI FJ00035T represents a new species of the genus Chelativorans, for which the name Chelativorans salis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI FJ00035T (=KCTC 92251T=CGMCC 1.19480T).
Audio-visual concert performances synchronize an audience’s heart rates
Authors: Czepiel Anna M. , Fink Lauren K. , Scharinger Mathias , Seibert Christoph , Wald-Fuhrmann Melanie , Kotz Sonja A.
Published: April 2024

People enjoy engaging with music. Live music concerts provide an excellent option to investigate real-world music experiences, and at the same time, use neurophysiological synchrony to assess dynamic engagement. In the current study, we assessed engagement in a live concert setting using synchrony of cardiorespiratory measures, comparing inter-subject, stimulus-response, correlation, and phase coherence. As engagement might be enhanced in a concert setting byseeingmusicians perform, we presented audiences with audio-only (AO) and audio-visual (AV) piano performances. Only correlation measures were above chance level. In comparing time-averaged synchrony across conditions, AV performances evoked higher inter-subject correlation of heart rate (ISC-HR). However, self-reported engagement did not correspond to synchrony when averaged across music pieces. On the other hand, time-resolved analyses show that synchronized deceleration-acceleration heart rate (HR) patterns, typical of an ‘orienting response’ (an index of directed attention), occurredwithinmusic pieces at salient events of section boundaries. That is, seeing musicians perform heightened audience engagement at structurally important moments in Western classical music. Overall, we could show that multisensory information shapes dynamic engagement. By comparing different synchrony measures, we further highlight the advantages of timeseries analysis, specifically ISC-HR, as a robust measure of holistic musical listening experiences in naturalistic concert settings.
Pleasurable music activates cerebral μ-opioid receptors: A combined PET-fMRI study
Authors: Putkinen Vesa , Seppälä Kerttu , Harju Harri , Hirvonen Jussi , Karlsson Henry K. , Nummenmaa Lauri
Published: April 2024

The μ-opioid receptor (MOR) system mediates incentive motivation and the hedonic component of primary rewards such as food and sex. However, there is no directin vivoevidence for the involvement of the MOR system in pleasure derived from aesthetic rewards such as music. We measured MOR activation with positron emission tomography (PET) and the agonist radioligand [11C] carfentanil with high affinity for MORs during the listening of pleasurable music and neutral baseline condition. Haemodynamic responses to pleasurable music were measured using functional magnetic resonance imaging (fMRI). The PET results revealed that pleasurable music increased [11C]carfentanil binding in several cortical and subcortical regions, including ventral striatum and orbitofrontal cortex, known to contain “hedonic hotspots”. Individual variation in baseline MOR tone influenced pleasure-dependent haemodynamic responses during music listening in regions associated with interoceptive, sensorimotor, and reward processing. Our results provide the first-ever neuroimaging evidence that listening to pleasurable music modulates MOR system activation and indicate that the μ-opioid system governs complex aesthetic rewards in addition to biologically salient primary rewards.
Diversity of the non-biting midges (Diptera: Chironomidae) in continental salt marshes in Serbia
Authors: Stamenković Olivera , Čerba Dubravka , Đurđević Aca , Koh Miran
Published: April 2024

Continental salt marshes represent specific inland saltwater bodies with unique ecological characteristics a fact that is mirrored by specific flora and fauna. However, there is still limited data on their biota in Serbia, which is especially true for aquatic macroinvertebrates, including chironomids (Diptera: Chironomidae). Here we investigated diversity and seasonal variations of chironomid community in six salt marshes distributed in the northern and southern part of Serbia. We recorded a total of 25 species, of which two are new for the Serbian chironomid fauna. Most of the recorded species are common in freshwaters and several of them are halotolerant. Chironomid community structure fluctuated in relation to the seasons. The highest diversity was recorded in the spring and summer months for the majority of studied salt marshes. The present findings should contribute to the knowledge of the faunistic composition of salt marshes in Serbia and provide a basis for future distributional and ecological studies of chironomids.
Extracellular vesicles from preeclampsia disrupt the blood-brain barrier via reduced claudin-5: potential role of vascular endothelial growth factor
Authors: Sandoval Hermes , Ibañez Belén , Contreras Moisés , Troncoso Felipe , Castro Fidel O , Caamaño Diego , Mendez Lidice , Escudero-Guevara Estefanny , Mistry Hiten D. , Kurlak Lesia O. , Vatish Manu , Acurio Jesenia , Escudero Carlos
Published: April 2024

Background

Physiopathology of life-treating cerebrovascular complications in preeclampsia are yet unknown. We investigated whether disruption of the blood-brain barrier (BBB), generated using circulating small extracellular vesicles (sEVs) from women with preeclampsia or placentae cultured under hypoxic conditions, impairs the expression of tight junction proteins, such as claudin 5 (CLDN5), mediated by VEGF and activation of VEGF receptor 2 (KDR).

Methods

sEVs were isolated from plasma (normal pregnancy, sEVs-NP, n=9); preeclampsia, sEVs-PE, n=9) or placental explants from normotensive pregnancies, cultured in normoxia (sEVs-Nor, n=10) or hypoxia (sEVs-Hyp, n=10). The integrity of the BBB was evaluated usingin vitro(human and mice brain endothelial cell lines) andin vivo(non-pregnant C57BL/6 mice (4 to 5 months old, (n=10) were injected with sEVs-Hyp), models.

Results

sEVs-PE and sEVs-Hyp reduced CLND5 levels (p<0.05) in the endothelial cell membrane without affecting other tight junction proteins. These results were negated with sEVs-PE sonication. sEVs-Hyp injected into non-pregnant mice generated neurological deficits and BBB disruption, specifically in the posterior area of the brain, associated with reduction in CLND5 levels in the brain cortex. Furthermore, sEVs-PE and sEVs-sHyp had higher VEGF levels than sEVs-NP and sEVs-Nor, respectively. Human brain endothelial cells exposed to sEVs-PE or sEVs-sHyp exhibited a reduction in the activation of KDR.

Conclusion

sEVs from hypoxic placentae and plasma from women with preeclampsia disrupt the BBB, via reduction of CLDN5, a phenomenon that may involve VEGF contained within these vesicles. These findings will improve the elucidation of cerebrovascular alterations in women with preeclampsia.
A Meta-Review about Medical 3D Printing
Authors: Meister Melissa , Luijten Gijs , Gsaxner Christina , Xie Kunpeng , Gruber Lennart J. , Li Jianning , Pepe Antonio , Li Yao , Rashad Ashkan , Seibold Constantin , Bahnsen Fin H. , Kim Moon , Fijačko Nino , Hölzle Frank , Sallam Malik , Röhrig Rainer , Štiglic Gregor , Keyl Julius , Kleesiek Jens , Alves Victor , Chen Xiaojun , Puladi Behrus , Egger Jan
Published: April 2024

In recent years, 3D printing (3DP) has gained importance in various fields. This technology has numerous applications, particularly in medicine. This contribution provides an overview on the state of the art of 3DP in medicine and showcases its current use in different medical disciplines and for medical education. In this meta-review, we provide a detailed listing of systematic reviews on this topic as this technology has become increasingly applied in modern medicine. We identified 134 relevant systematic reviews on medical 3DP in the medical search engine PubMed until 2023. 3DP has applications in various medical specialties, but is mainly used in orthopedics, oral and maxillofacial surgery, dentistry, cardiology and neurosurgery. In surgical contexts, the adoption of 3DP contributes to a reduction in operation time, reduced blood loss, minimized fluoroscopy time and an overall improved surgical outcome. Nevertheless, the primary use of 3DP is observed in non-invasive applications, particularly in the creation of patient-specific models (PSM). These PSMs enhance the visualization of patients’ anatomy and pathology, thereby facilitating surgical planning and execution, medical education and patient counseling. The current significance of 3DP in medicine offers a compelling perspective on the potential for more individualized and personalized medical treatments in the future.
Diagnostic Performance of Claude 3 from Patient History and Key Images in Diagnosis Please Cases
Authors: Kurokawa Ryo , Ohizumi Yuji , Kanzawa Jun , Kurokawa Mariko , Kiguchi Takao , Gonoi Wataru , Abe Osamu
Published: April 2024

Backgrounds

Large language artificial intelligence models have showed its diagnostic performance based solely on textual information from clinical history and imaging findings. However, the extent of their performance when utilizing radiological images and providing differential diagnoses has yet to be investigated.

Purpose

We employed the latest version of Claude 3, Opus, released on March 4, 2024, to investigate its diagnostic performance in answering Radiology’s Diagnosis Please quiz questions under three conditions: (1) when provided with clinical history alone; (2) when given clinical history along with imaging findings; and (3) when supplied with clinical history and key images.

Furthermore, we evaluated the diagnostic performance of the model when instructed to list differential diagnoses.

Materials and Methods

Claude 3 Opus was tasked with listing the primary diagnosis and two differential diagnoses for 322 quiz questions from Radiology’s “Diagnosis Please” cases, which included cases 1 to 322, published from 1998 to 2023. The analyses were carried out under the following input conditions:

Condition 1: Submitter-provided clinical history (text) alone

Condition 2: Submitter-provided clinical history and imaging findings (text) Condition 3: Submitter-provided clinical history (text) and key images (PDF files)

We applied McNemar’s tests to evaluate differences in correct response rates for primary diagnoses across Conditions 1, 2, and 3.

Results

The correct primary diagnoses rates were 62/322 (19.3%), 178/322 (55.3%), and 93/322 (28.8%) for Conditions 1, 2, and 3, respectively. Additionally, Claude 3 Opus accurately provided the correct answer as a differential diagnosis in up to 22/322 (6.8%) of cases. There were statistically significant differences in correct response rates for primary diagnoses between all combinations of Conditions 1, 2, and 3 (p<0.001).

Conclusion

Claude 3 Opus demonstrated significantly improved diagnostic performance by inputting key images in addition to clinical history. The ability to list important differential diagnoses was also confirmed.

Key Results

This study investigated Claude 3 Opus’s performance in Radiology Diagnosis Please Cases using clinical history, key images, and imaging findings.

Key images or imaging findings inputs significantly improved correct primary diagnoses from 19.3% to 28.8% or 55.5%, respectively.

By having two additional differential diagnoses presented, total correct responses improved by 3.1–6.8%.

Summary statement

Large language AI model Claude 3 Opus demonstrated significantly improved diagnostic accuracy by adding key images with clinical history compared with clinical history alone.
Contactless metabolism estimation of small animals using high-frequency millimeter-wave radar
Authors: Ono Hiroaki , Ishikawa Kiyomi , Wataki Ayaka , Fujino Shoko , Sunagawa Genshiro A.
Published: April 2024

Animals flexibly adapt to internal and external environmental changes by utilizing energy produced from oxygen as fuel. By non-invasively monitoring an animal’s oxygen consumption, it becomes possible to understand an individual’s metabolic state. Calorimeters are known for directly measuring oxygen consumption but come with the issue of high initial costs. Despite the development of non-invasive techniques for measuring vital signs—including respiration rate (RR), heart rate (HR), and body temperature (Tb)—as indicators of metabolism, conventional methods encounter difficulties in estimating oxygen consumption rate (VO2). In this study, we developed a system that estimates the oxygen consumption of small animals using signals obtained from millimeter wave (mm-wave) radar technology processed through machine learning. By identifying frequency bands within the mm-wave signals contributing to VO2, our system is capable of predicting oxygen consumption several minutes in advance. Our system enables contactless, low-cost and multiplexed measurements of oxygen consumption, presenting a significant advancement in the field.
Bioinformatics Copilot 1.0: A Large Language Model-powered Software for the Analysis of Transcriptomic Data
Authors: Wang Yongheng , Zhang Weidi , Lin Siyu , Farruggio Matthew S. , Wang Aijun
Published: April 2024

The field of single-cell transcriptomics has been producing extensive datasets, advancing our understanding of cellular functions in various tissues, and empowering diagnosis, prognosis, and drug development. However, parsing through this data has been a monumental task, often stretching weeks to months. This bottleneck arises due to the sheer volume of data generated—ranging from hundreds of gigabytes to tens of terabytes—that demands extensive time for analysis. Moreover, the data analysis involves an intricate series of steps utilizing various software packages, creating a steep learning curve for biologists. Additionally, the iterative nature of data analysis in this domain necessitates a deep biological insight to formulate relevant questions, conduct analysis, interpret results, and refine hypotheses. This iterative loop has required close collaboration between biologists and bioinformaticians, which is hampered by protracted communication cycles. To address these challenges, we present a large language model-powered software, Bioinformatics Copilot 1.0. It allows users to analyze data through an intuitive natural language interface, without requiring proficiency in programming languages such as Python or R. It is engineered for cross-platform functionality, with support for Mac, Windows, and Linux. Importantly, it facilitates local data analysis, ensuring adherence to stringent data management regulations that govern the use of patient samples in medical and research institutions. We anticipate that this tool will expedite the data analysis workflow in numerous research endeavors, thereby accelerating advancements in the biomedical sciences.
Enhancing predictions of protein stability changes induced by single mutations using MSA-based Language Models
Authors: Cuturello Francesca , Celoria Marco , Ansuini Alessio , Cazzaniga Alberto
Published: April 2024

Protein Language Models offer a new perspective for addressing challenges in structural biology, while relying solely on sequence information. Recent studies have investigated their effectiveness in forecasting shifts in thermodynamic stability caused by single amino acid mutations, a task known for its complexity due to the sparse availability of data, constrained by experimental limitations. To tackle this problem, we introduce two key novelties: leveraging a Protein Language Model that incorporates Multiple Sequence Alignments to capture evolutionary information, and using a recently released mega-scale dataset with rigorous data pre-processing to mitigate overfitting. We ensure comprehensive comparisons by fine-tuning various pre-trained models, taking advantage of analyses such as ablation studies and baselines evaluation. Our methodology introduces a stringent policy to reduce the widespread issue of data leakage, rigorously removing sequences from the training set when they exhibit significant similarity with the test set. The MSA Transformer emerges as the most accurate among the models under investigation, given its capability to leverage co-evolution signals encoded in aligned homologous sequences. Moreover, the optimized MSA Transformer outperforms existing methods and exhibits enhanced generalization power, leading to a notable improvement in predicting changes in protein stability resulting from point mutations. Code and data are available athttps://github.com/RitAreaSciencePark/PLM4Muts.
Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally
Authors: Zhao Rui , Ren Baihui , Xiao Yujie , Tian Jifeng , Zou Yi , Wei Jiafan , Qi Yanqing , Hu Ankang , Xie Xiaoying , Huang Z. Josh , Shu Yousheng , He Miao , Lu Jiangteng , Tai Yilin
Published: April 2024

The stability of functional brain network is maintained by homeostatic plasticity, which restores equilibrium following perturbation. As the initiation site of action potentials, the axon initial segment (AIS) of glutamatergic projection neurons (PyNs) undergoes dynamic adjustment that exerts powerful control over neuronal firing properties in response to changes in network states. Although AIS plasticity has been reported to be coupled with the changes of network activity, it is poorly understood whether it involves direct synaptic input to the AIS. Here we show that changes of GABAergic synaptic input to the AIS of cortical PyNs, specifically from chandelier cells (ChCs), are sufficient to drive homeostatic tuning of the AIS within 1-2 weeks, while those from parvalbumin-positive basket cells do not. This tuning is reflected in the morphology of the AIS, the expression level of voltage-gated sodium channels, and the intrinsic neuronal excitability of PyNs. Interestingly, the timing of AIS tuning in PyNs of the prefrontal cortex corresponds to the recovery of changes in social behavior caused by alterations of ChC synaptic transmission. Thus, homeostatic plasticity of the AIS at postsynaptic PyNs may counteract deficits elicited by imbalanced ChC presynaptic input.

Teaser

Axon initial segment dynamically responds to changes in local input from chandelier cells to prevent abnormal neuronal functions.
psudo: Exploring Multi-Channel Biomedical Image Data with Spatially and Perceptually Optimized Pseudocoloring
Authors: Warchol Simon , Troidl Jakob , Muhlich Jeremy , Krueger Robert , Hoffer John , Lin Tica , Beyer Johanna , Glassman Elena , Sorger Peter K. , Pfister Hanspeter
Published: April 2024

Over the past century, multichannel fluorescence imaging has been pivotal in myriad scientific breakthroughs by enabling the spatial visualization of proteins within a biological sample. With the shift to digital methods and visualization software, experts can now flexibly pseudocolor and combine image channels, each corresponding to a different protein, to explore their spatial relationships. We thus proposepsudo, an interactive system that allows users to create optimal color palettes for multichannel spatial data. Inpsudo, a novel optimization method generates palettes that maximize the perceptual differences between channels while mitigating confusing color blending in overlapping channels. We integrate this method into a system that allows users to explore multi-channel image data and compare and evaluate color palettes for their data. An interactive lensing approach provides on-demand feedback on channel overlap and a color confusion metric while giving context to the underlying channel values. Color palettes can be applied globally or, using the lens, to local regions of interest. We evaluate our palette optimization approach using three graphical perception tasks in a crowdsourced user study with 150 participants, showing that users are more accurate at discerning and comparing the underlying data using our approach. Additionally, we showcasepsudoin a case study exploring the complex immune responses in cancer tissue data with a biologist.

CCS Concepts

Human-centered computing→Visualization systems and tools;
Simultaneous cortical, subcortical, and brainstem mapping of sensory activation
Authors: Reddy Neha A. , Clements Rebecca G. , Brooks Jonathan C. W. , Bright Molly G.
Published: April 2024

Non-painful tactile sensory stimuli are processed in the cortex, subcortex, and brainstem. Recent functional magnetic resonance imaging (fMRI) studies have highlighted the value of whole-brain, systems-level investigation for examining pain processing. However, whole-brain fMRI studies are uncommon, in part due to challenges with signal to noise when studying the brainstem. Furthermore, the differentiation of small sensory brainstem structures such as the cuneate and gracile nuclei necessitates high resolution imaging. To address this gap in systems-level sensory investigation, we employed a whole-brain, multi-echo fMRI acquisition at 3T with multi-echo independent component analysis (ME-ICA) denoising and brainstem-specific modeling to enable detection of activation across the entire sensory system. In healthy participants, we examined patterns of activity in response to non-painful brushing of the right hand, left hand, and right foot, and found the expected lateralization, with distinct cortical and subcortical responses for upper and lower limb stimulation. At the brainstem level, we were able to differentiate the small, adjacent cuneate and gracile nuclei, corresponding to hand and foot stimulation respectively. Our findings demonstrate that simultaneous cortical, subcortical, and brainstem mapping at 3T could be a key tool to understand the sensory system in both healthy individuals and clinical cohorts with sensory deficits.
MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability
Authors: Jasani Neel , Xu Xiaonan , Posorske Benjamin , Kim Yumi , Vera Olga , Tsai Kenneth Y. , DeNicola Gina M. , Karreth Florian A.
Published: April 2024

ABSTRACT

Overexpression of PHGDH, the rate-limiting enzyme in the serine synthesis pathway, promotes melanomagenesis, melanoma cell proliferation, and survival of metastases in serine-low environments such as the brain. WhilePHGDHamplification explains PHGDH overexpression in a subset of melanomas, we find that PHGDH levels are universally increased in melanoma cells due to oncogenic BRAFV600EpromotingPHGDHtranscription through mTORC1-mediated translation of ATF4. Importantly, PHGDH expression was critical for melanomagenesis as depletion ofPHGDHin genetic mouse models blocked melanoma formation. Despite BRAFV600E- mediated upregulation, PHGDH was further induced by exogenous serine restriction. Surprisingly, BRAFV600Einhibition diminished serine restriction-mediated PHGDH expression by preventing ATF4 induction, creating a potential vulnerability whereby melanoma cells could be specifically starved of serine by combining BRAFV600Einhibition with exogenous serine restriction. Indeed, we show that this combination promoted cell death in vitro and attenuated melanoma growth in vivo. This study identified a melanoma cell-specific PHGDH-dependent vulnerability.
Demixer: A probabilistic generative model to delineate different strains of a microbial species in a mixed infection sample
Authors: Brintha VP , Narayanan Manikandan
Published: April 2024

Motivation

Multi-drug resistant or hetero-resistant Tuberculosis (TB) hinders the successful treatment of TB. Hetero-resistant TB occurs when multiple strains of the TB-causing bacterium with varying degrees of drug susceptibility are present in an individual. Existing studies predicting the proportion and identity of strains in a mixed infection sample rely on a reference database of known strains. A main challenge then is to identifyde novostrains not present in the reference database, while quantifying the proportion of known strains.

Results

We present Demixer, a probabilistic generative model that uses a combination of reference-based and reference-free techniques to delineate mixed infection strains in whole genome sequencing (WGS) data. Demixer extends a topic model widely used in text mining to represent known mutations and discover novel ones. Parallelization and other heuristics enabled Demixer to process large datasets like CRyPTIC (Comprehensive Resistance Prediction for Tuberculosis: an International Consortium). In both synthetic and experimental benchmark datasets, our proposed method precisely detected the identity (e.g., 91.67% accuracy on the experimentalin vitrodataset) as well as the proportions of the mixed strains. In real-world applications, Demixer revealed novel high confidence mixed infections (101 out of 1,963 Malawi samples analyzed), and new insights into the global frequency of mixed infection (2% at the most stringent threshold in the CRyPTIC dataset) and its significant association to drug resistance. Our approach is generalizable and hence applicable to any bacterial and viral WGS data.

Availability

All code relevant to Demixer is available athttps://github.com/BIRDSgroup/Demixer.

Contact

nmanik@cse.iitm.ac.in

Supplementary information

The Supplemental Data/Result Files related to Demixer are available at this link:https://drive.google.com/drive/folders/13WFACrn2EpeVTO7533-YwlAGjgF4UH3k?usp=drive_link.
Detection of Microsatellite Instability in Colorectal Cancer Tissue and Plasma samples using a new Multiplex Droplet Digital PCR kit
Authors: Evrard Camille , Chaba Kariman , Abdelli Justine , Garinet Simon , Blons Helene , Zaanan Aziz , Bachet Jean-Baptiste , Benhaim Leonor , Mulot Claire , Didelot Audrey , Corre Delphine Le , Lukban Jerianne , Yin Jennifer , Corner Adam , Ho Mai , Taly Valérie , Tougeron David , Laurent-Puig Pierre
Published: April 2024

Management of colorectal cancer (CRC) patients relies on the accurate determination of microsatellite instability (MSI) status. MSI status can have an influence on therapy decisions centered on immune checkpoint inhibitors. In this study a novel droplet digital PCR (ddPCR) kit for MSI status determination was validated across 2 separate CRC patient cohorts: 102 tumor samples from the ALGECOLS cohort and 129 plasma samples from the RASANC cohort. Each cohort was assessed for MSI status using the novel ddPCR kit and compared to historical and/or newly obtained results, (either immunohistochemistry analysis or PCR amplification). Concordance between ddPCR and conventional MSI determination methods for the analysis of tissue samples was 97.1% for ALGECOLS. When looking at positive ctDNA samples, a strong concordance was observed for the RASANC cohort. This study illustrates that ddPCR MSI testing represents a rapid, sensitive and accurate method with a strong correlation to established methods. Moreover, the ability of the described approach to monitor MSI status in both tumor and plasma enhances the potential for the use of MSI status in longitudinal monitoring of CRC patients.
Deaths averted by COVID-19 vaccination in select Latin American and Caribbean Countries: a modelling study
Authors: Savinkina Alexandra , Weinberger Daniel M. , Toscano Cristiana M. , De Oliveira Lucia H.
Published: April 2024

Background

The COVID-19 pandemic has had a significant impact on global health, with millions of lives lost worldwide. Vaccination has emerged as a crucial strategy in mitigating the impact of the disease. This study aims to estimate the number of deaths averted through vaccination in LAC during the first year and a half of vaccination rollout (January 2021 - May 2022).

Methods

Publicly available data on COVID-19 deaths and vaccination rates were used to estimate the total number of deaths averted via vaccination in LAC. Using estimates for number of deaths, number of vaccinated, and vaccine effectiveness, a counterfactual estimated number of deaths observed without vaccination was calculated. Vaccine effectiveness estimates were obtained from published studies. The analysis focused on 17 countries in LAC and considered adults aged 18 years and above.

Findings

After accounting for underreporting, the analysis estimated that over 1.49 million deaths were caused by COVID-19 in the selected countries during the study period. Without vaccination, the model estimated that between 2.10 and 4.11 million COVID-19 deaths would have occurred. Consequently, vaccination efforts resulted in approximately 610,000 to 2.61 million deaths averted.

Interpretation

This study represents the first large-scale, multi-center estimate of population-level vaccine impact on COVID-19 mortality in LAC. The findings underscore the substantial impact of timely and widespread vaccination in averting COVID-19 deaths. These results provide crucial support for vaccination programs aimed at combating epidemic infectious diseases in the region and future pandemics.

Funding

This study was funded by the Pan-American Health Organization (PAHO).