bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicentre evaluation of the NG-test DetecTool OXA-23 for the rapid detection of OXA-23 carbapenemase directly from blood cultures
Authors: Vasilakopoulou Alexandra , Naas Thierry , Gonzalez Camille , Vila Jordi , Szabo Dóra , Riccobono Eleonora , Kamotsay Katalin , Reissier Sophie , Berbel Dàmaris , Aszalos Albert Zoltan , Rosenmoller Magda , Stankov-Puges Milovan , Georgiou Panagiota-Christina , Vourli Sophia , Volland Hervé , Pournaras Spyros
Published: March 2024

Objectives

A multicentre study evaluating NG-Test DetecTool OXA-23 for the detection of OXA-23 carbapenemase directly from positive blood cultures (PBCs).

Methods

The NG-Test DetecTool OXA-23 is an immunoassay that integrates a sample preparation device. We evaluated NG-Test DetecTool OXA-23 on 189 spiked and 126 clinical PBCs. The clinical samples’ standard-of-care procedure consisted of bacterial identification from the first day of positivity by MALDI-TOF MS, conventional culture and antimicrobial susceptibility testing. The immunoassay results were verified molecularly. The strains used for the spiked samples consisted of well-characterized Acinetobacter baumannii and Proteus mirabilis strains.

Results

The NG-Test DetecTool OXA-23 was evaluated on 315 PBCs and revealed sensitivity of 100% (95% CI: 98.21%–100.00%) and specificity of 100% (95% CI: 96.73%–100.00%). It provided 204 true-positive results for OXA-23 in 196 bottles with carbapenem-resistant A. baumannii (CRAB) and 8 bottles with carbapenem-resistant P. mirabilis and also provided 111 true-negative results. There were no false-positive and no false-negative results. Among the 315 PBCs studied, 83 clinical blood cultures collected in the ICU of a Greek university hospital, which were tested prospectively, all yielded CRAB, and OXA-23 was correctly detected in all samples from the first day of positivity using the NG-Test DetecTool OXA-23.

Conclusions

The NG-Test DetecTool OXA-23 has exhibited excellent sensitivity and specificity for OXA-23 detection in PBCs and can provide valuable information for appropriate selection of antibiotic therapy and early implementation of infection control measures.
Clinically Relevant Laboratory Monitoring of Gender-Affirming Hormone Therapy in Transgender People—Experiences from a Teaching Hospital in the Netherlands
Authors: Pouw Nadine , van der Linden Joke , Teuben Sonja , Kos Snježana
Published: March 2024

Background

Transgender care is shifting from academic to nonacademic settings leading to use of common (immunoassay) compared to sophisticated (mass spectrometry) methods to monitor estradiol and testosterone during gender-affirming hormone therapy (GAHT). The type of assay can influence results and have significant implications for clinical decision making. An evidence gap is present in recommendations regarding the assay needed to monitor GAHT. The present study aimed to summarize current evidence and evaluate immunoassay estradiol and testosterone concentrations in transgender people visiting a nonacademic hospital for GAHT.

Methods

Clinical practice guidelines on GAHT and scientific literature on assay methodologies were screened and summarized. Laboratory and medical data from 252 patients who visited the transgender outpatient clinic of the Maasstad Hospital for GAHT between 2020 and 2022 were retrospectively analyzed.

Results

Our research showed that the most used clinical practice guidelines for GAHT provide hormonal target values without recommending a preferred method. A comprehensive literature search on agreement between immunoassay and mass spectrometry showed substantial heterogeneity in results. Retrospective analysis of our immunoassay measured data in transgender people showed hormonal changes during GAHT that are to be expected from the medication used.

Conclusions

We demonstrate that laboratory monitoring of GAHT in a nonacademic hospital can be done safely by immunoassay in most cases. Only in cases where clinical observation is discordant with the hormonal results do more sophisticated methods need to be deployed. A best practice model was proposed for transgender care in nonacademic hospitals.
Digital health technologies for high-risk pregnancy management: three case studies using Digilego framework
Authors: Myneni Sahiti , Zingg Alexandra , Singh Tavleen , Ross Angela , Franklin Amy , Rogith Deevakar , Refuerzo Jerrie
Published: March 2024

Objective

High-risk pregnancy (HRP) conditions such as gestational diabetes mellitus (GDM), hypertension (HTN), and peripartum depression (PPD) affect maternal and neonatal health. Patient engagement is critical for effective HRP management (HRPM). While digital technologies and analytics hold promise, emerging research indicates limited and suboptimal support offered by the highly prevalent pregnancy digital solutions within the commercial marketplace. In this article, we describe our efforts to develop a portfolio of digital products leveraging advances in social computing, data science, and digital health.

Methods

We describe three studies that leverage core methods from Digilego digital health development framework to (1) conduct large-scale social media analysis (n = 55 301 posts) to understand population-level patterns in women’s needs, (2) architect a digital repository to enable women curate HRP related information, and (3) develop a digital platform to support PPD prevention. We applied a combination of qualitative coding, machine learning, theory-mapping, and programmatic implementation of theory-linked digital features. Further, we conducted preliminary testing of the resulting products for acceptance with sample of pregnant women for GDM/HTN information management (n = 10) and PPD prevention (n = 30).

Results

Scalable social computing models using deep learning classifiers with reasonable accuracy have allowed us to capture and examine psychosociobehavioral drivers associated with HRPM. Our work resulted in two digital health solutions, MyPregnancyChart and MomMind are developed. Initial evaluation of both tools indicates positive acceptance from potential end users. Further evaluation with MomMind revealed statistically significant improvements (P < .05) in PPD recognition and knowledge on how to seek PPD information.

Discussion

Digilego framework provides an integrative methodological lens to gain micro-macro perspective on women’s needs, theory integration, engagement optimization, as well as subsequent feature and content engineering, which can be organized into core and specialized digital pathways for women engagement in disease management.

Conclusion

Future works should focus on implementation and testing of digital solutions that facilitate women to capture, aggregate, preserve, and utilize, otherwise siloed, prenatal information artifacts for enhanced self-management of their high-risk conditions, ultimately leading to improved health outcomes.
Polymorphisms in two key anthocyanic genes of clivia (Clivia miniata L.) reveal evidence of selection and possible association with flower pigmentation
Authors: Maleka Mathabatha F , Spies Johan J
Published: March 2024

Members of the genus Clivia show considerable variation in flower pigmentation and morphology. Such variation is affected by mutations that emerge in candidate flower development genes over time. Besides population history, mutations can further illuminate the effects of demographic events in populations in addition to population genetic parameters including selection, recombination, and linkage disequilibrium (LD). The current study aimed to find sequence variants in 2 anthocyanin biosynthetic genes (DFR and bHLH) of Clivia miniata and use the data to assess population genetic factors from a random collection of orange/red- and yellow-flowered specimens. Overall, average nucleotide diversity in the 2 anthocyanin genes was moderate (π = 0.00646), whereas haplotypes differed significantly (Hd ≥ 0.9). Gene evolution was seemingly driven by mutations (CmiDFR) or recombinations (CmibHLH001). LD decayed swiftly within the analyzed gene regions and supported the feasibility of assessing trait-variant associations via the association/linkage mapping approach. In the end, most associations were found to be spurious, but 1 haplotype in CmibHLH001 showed a promising correlation to the orange/red flower phenotype in Clivia specimens. In all, the present study is the first to measure gene-level diversity in C. miniata—data that had never been reported so far. Furthermore, the study also identified allelic and haplotypic variants that may be beneficial in future association genetic studies of Clivia. Such studies, however, consider large diverse populations to control for statistical bias intrinsic to the analysis of small datasets.
Indirect genetic effects should make group size more evolvable than expected
Authors: Fisher David N
Published: March 2024

Group size is an important trait for many ecological and evolutionary processes. However, it is not a trait possessed by individuals but by social groups, and as many genomes contribute to group size understanding its genetic underpinnings and so predicting its evolution is a conceptual challenge. Here I suggest how group size can be modelled as a joint phenotype of multiple individuals, and so how models for evolution accounting for indirect genetic effects are essential for understanding the genetic variance of group size. This approach makes it clear that (a) group size should have a larger genetic variance than initially expected as indirect genetic effects always contribute exactly as much as direct genetic effects and (b) the response to selection of group size should be faster than expected based on direct genetic variance alone as the correlation between direct and indirect effects is always at the maximum positive limit of 1. Group size should therefore show relatively rapid evolved increases and decreases, the consequences of which and evidence for I discuss.
Modeling, driving characterization of collision and stick-slip vibration-driven system
Authors: Liu Tao , Wu Shaopei , Li Guofang , Li Deyang , You Taiwen , Ding Wangcai
Published: March 2024

Considering the internal collision vibration-driven and external discontinuous resistance tolerance fusion conditions, the non-smooth dynamics characteristics of collision and stick-slip vibration-driven system are studied and experimented. Unilateral collision behavior of internal oscillators under the action of a periodic force to achieve system motion in different directions, it overcome the external Coulomb friction force and drives the system to drive in steady state under a certain direction. The kinematic and dynamic models of the system are established, and the collision and stick-slip driving motion of the system is analyzed based on the theory of non-smooth dynamics. The voice coil motor is used as the internal driving element, and the vibration driving test platform is designed and fabricated, and the driving characteristics of the system are studied experimentally. The study shows that there are three forms of movement in the steady state driving motion of the system: sticking motion, forward motion and backward motion; sine wave excitation and triangular wave excitation as input excitation have the characteristic of smoother operation with less shock; external excitation parameter regulation can change the system speed and direction of the movement; excitation frequency as a regulation parameter has the advantages of speed bandwidth, continuity, and so on; the system average driving speed in the numerical simulation and experimental test with the system average driving speed in numerical simulation and experimental test has the same rule of change, the backward motion is located in the low-frequency region, the forward motion is located in the high-frequency region, the friction coefficient and the excitation amplitude affect the size of driving speed. The results and methods of this study provide a corresponding theoretical basis for the design and parameter optimization of vibration-driven robots.
Robotic excision of a retrocaval ancient schwannoma: a case report
Authors: Marquez Bianca , Luciano Emmanuel , Ghanem Maher
Published: March 2024

We report a case of a robotic-assisted excision of a retrocaval ancient schwannoma. A 40-year-old female presented with generalized weakness and abdominal pain that led to the diagnosis of a retroperitoneal mass adjacent to the pancreas and inferior vena cava. Because of the clinical, imaging, and needle biopsy findings, the patient underwent an elective robotic-assisted retroperitoneal exploration. We provide an overview of the pathology and highlight the significance of utilizing a minimally invasive approach for excision of retroperitoneal masses.
Non-Hodgkin lymphoma
Authors: Bhatt Vijaya Raj , Armitage James O.
Published: March 2024

Non-Hodgkin lymphomas comprise precursor lymphoid neoplasms, mature B-cell neoplasms, and mature T-cell neoplasms. The aetiology of most cases is unknown, but increased risk is associated with immune deficiencies, agricultural chemicals, autoimmune disorders, treated Hodgkin lymphoma, and some infectious agents. Incidence varies from 10 to 22 cases per 100 000 per year in different populations. Patients with non-Hodgkin lymphoma most commonly present with lymphadenopathy, but other presentations include systemic symptoms or those attributable to mediastinal or retroperitoneal masses or involvement. Diagnosis is typically based on expert evaluation of an adequate lymph node biopsy. Staging depends largely on determining the anatomical extent of disease, with FDG positron emission tomography/CT scanning generally the preferable imaging modality. For most patients, the goal of therapy is to achieve a complete remission. Patients with potentially curable lymphomas, such as diffuse large B-cell lymphoma and Burkitt’s lymphoma, are almost always treated promptly with intensive regimens, for example, chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone) plus the anti-CD20 monoclonal antibody rituximab. By contrast, follicular lymphoma is often not curable and the best treatment is not clear, with many physicians favouring no initial therapy in an asymptomatic patient. Patients who are not cured with initial therapy are candidates for what has been termed ‘salvage therapy’. For most patients, the only curative approach in this setting is haematopoietic stem cell transplantation, the toxicity of which means that it is only sensibly offered to carefully selected patients. In recent years, anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have emerged as important options for management of several types of relapsed B-cell lymphomas. These CAR T-cell therapies are replacing the use of transplantation in many patients. Various new agents, such as small molecule kinase and BCL-2 inhibitors, provide additional options for salvage therapy and hope for prolonging survival.
Osteoporosis and osteopenia in patients with psoriatic arthritis: A single-centre retrospective study
Authors: Takami Kenji , Higashiyama Mari , Tsuji Shigeyoshi
Published: March 2024

Objective

It is known that fracture risk is increased in patients with psoriatic arthritis (PsA); however, there is no consensus on the association with osteoporosis. The purpose of this study was to elicit the rate of osteoporosis and the risk factors of osteoporosis in patients with PsA at our institution.

Methods

The data in this study were extracted from 163 patients with PsA. Osteoporosis and osteopenia were defined based on the WHO definition. Osteoporosis was also diagnosed when a fragility vertebral compression fracture was observed.

Results

The osteoporosis and osteopenia rates for PsA patients were 11.7% and 33.1%, respectively. The rates of osteoporosis and osteopenia in males were particularly high compared to previous reports, at 9.3% and 34.3%, respectively. Trabecular bone score was considered age-appropriate for both males and females. Body mass index and Trabecular bone score were significantly lower in patients with osteoporosis.

Conclusions

In patients with PsA, males are at elevated risk of osteoporosis and associated fragility fractures even if they are under 50 years. Body mass index was significantly lower in osteoporotic cases, suggesting the importance of bone mineral density testing and treatment in such cases.
Sources of richness and ineffability for phenomenally conscious states
Authors: Ji Xu , Elmoznino Eric , Deane George , Constant Axel , Dumas Guillaume , Lajoie Guillaume , Simon Jonathan , Bengio Yoshua
Published: March 2024

Conscious states—state that there is something it is like to be in—seem both rich or full of detail and ineffable or hard to fully describe or recall. The problem of ineffability, in particular, is a longstanding issue in philosophy that partly motivates the explanatory gap: the belief that consciousness cannot be reduced to underlying physical processes. Here, we provide an information theoretic dynamical systems perspective on the richness and ineffability of consciousness. In our framework, the richness of conscious experience corresponds to the amount of information in a conscious state and ineffability corresponds to the amount of information lost at different stages of processing. We describe how attractor dynamics in working memory would induce impoverished recollections of our original experiences, how the discrete symbolic nature of language is insufficient for describing the rich and high-dimensional structure of experiences, and how similarity in the cognitive function of two individuals relates to improved communicability of their experiences to each other. While our model may not settle all questions relating to the explanatory gap, it makes progress toward a fully physicalist explanation of the richness and ineffability of conscious experience—two important aspects that seem to be part of what makes qualitative character so puzzling.
Engineering surface framework TiO6 single sites for unprecedented deep oxidative desulfurization
Authors: Yu Shen , Liu Zhan , Lyu Jia-Min , Guo Chun-Mu , Yang Xiao-Yu , Jiang Peng , Wang Yi-Long , Hu Zhi-Yi , Sun Ming-Hui , Li Yu , Chen Li-Hua , Su Bao-Lian
Published: March 2024

Catalytic oxidative desulfurization (ODS) using titanium silicate catalysts has emerged as an efficient technique for the complete removal of organosulfur compounds from automotive fuels. However, the precise control of highly accessible and stable-framework Ti active sites remains highly challenging. Here we reveal for the first time by using density functional theory calculations that framework hexa-coordinated Ti (TiO6) species of mesoporous titanium silicates are the most active sites for ODS and lead to a lower-energy pathway of ODS. A novel method to achieve highly accessible and homogeneously distributed framework TiO6 active single sites at the mesoporous surface has been developed. Such surface framework TiO6 species exhibit an exceptional ODS performance. A removal of 920 ppm of benzothiophene is achieved at 60°C in 60 min, which is 1.67 times that of the best catalyst reported so far. For bulky molecules such as 4,6-dimethyldibenzothiophene (DMDBT), it takes only 3 min to remove 500 ppm of DMDBT at 60°C with our catalyst, which is five times faster than that with the current best catalyst. Such a catalyst can be easily upscaled and could be used for concrete industrial application in the ODS of bulky organosulfur compounds with minimized energy consumption and high reaction efficiency.
The impact of hamstring lengthening on stance knee flexion at skeletal maturity in ambulatory cerebral palsy
Authors: Kanashvili Bidzina , Niiler Timothy A. , Church Chris , Lennon Nancy , Shrader M. Wade , Howard Jason J. , Miller Freeman
Published: March 2024

This study reports the long-term outcomes of hamstring lengthening to treat flexed knee gait in children with ambulatory cerebral palsy (CP) after skeletal maturity. This retrospective longitudinal observational study used instrumented gait analysis (GA) <8 and >15 years old in children with bilateral CP. The primary variable was knee flexion in stance phase. Eighty children (160 limbs) were included; 49% were male, 51% female. Mean age at first GA was 6.0 (SD: 1.2) years and 19.6 (SD: 4.5) years at final GA. Mean follow-up was 13.7 (SD: 4.7) years. Children were classified as Gross Motor Function Classification System I-8, II-46 and III-26. Average Gross Motor Function Measure Dimension D was 72% (SD: 20%). Hamstring lengthenings occurred once in 82, twice in 54 and three times in 10 limbs. From initial to final GA, average knee flexion in stance was unchanged, 27.8° (SD: 14.8°) to final 27.0° (SD: 11.2°; P = 0.54). Knee flexion at foot contact was 39.6° (SD: 13.0°), improving to final GA of 30.7° (SD: 10.6°; P < 0.001). Initial gait deviation index was 65.8 (SD: 31.9), improving to final 78.9 (SD: 28.2; P < 0.001). Older age, males and concomitant plantar flexor lengthening predicted change toward more flexed knee gait. Hamstring lengthening did not lead to back-kneeing gait at maturity while maintaining childhood stance phase knee flexion. A subgroup still developed significant flexed knee gait posture and may have benefited from more aggressive treatment options. This outcome may also be impacted by diverse functional levels, etiologies and treatments of flexed knee gait.
Local Excision Versus Radical Resection for Grade 2 Rectal Neuroendocrine Tumors: A Multicenter Propensity Score-Matched Analysis
Authors: Zeng Xinyu , Zhang Rui , Jiang Weizhong , Li Chengguo , Yu Minhao , Liu Weizhen , Di Maojun , Wu Hongxue , Sun Yueming , Xiong Zhiguo , Jiang Congqing , Yu Bin , Zhou Shengning , Li Yong , Liao Xiaofeng , Xia Lijian , Zhang Wei , Lin Guole , Tao Kaixiong
Published: March 2024

BACKGROUND:

Studies on the grade 2 rectal neuroendocrine tumors are limited and the optimal treatment for these tumors is not well established.

OBJECTIVE:

To compare the oncologic results of local excision versus radical resection for the treatment of grade 2 rectal neuroendocrine tumors.

DESIGN:

Retrospective multicenter propensity score-matched study to minimize heterogeneity between groups and focus on the difference between surgery strategies.

SETTINGS:

Seventeen Chinese large-scale medical centers participated in this study.

PATIENTS:

A total of 144 patients with pathologically confirmed grade 2 rectal neuroendocrine tumors were retrospectively analyzed.

MAIN OUTCOME MEASURES:

Cancer-specific survival and relapse-free survival were assessed to compare surgery strategies.

RESULTS:

A total of 144 patients with grade 2 rectal neuroendocrine tumors were enrolled in this study. Twenty-seven patients underwent endoscopic resection, 55 underwent transanal excision, 50 underwent radical resection, and 12 underwent palliative surgery or biopsy for distant metastasis. Of the 50 patients who underwent radical resection, 30 (60.0%) had clinically positive lymph nodes based on the histopathology results. The optimal cutoff value for tumor size to predict cancer-specific survival was 1.5 cm. In patients with grade 2 rectal neuroendocrine tumors ≤ 1.5 cm, there were no significant differences in cancer-specific survival and relapse-free survival between local excision and radical resection groups (P >0.05). In patients with grade 2 rectal neuroendocrine tumors > 1.5 cm, relapse-free survival was significantly lower in the local excision group than in the radical resection group (P = 0.04).

LIMITATIONS:

The nature of retrospective review and relatively short follow-up period are limitations of this study.

CONCLUSIONS:

Grade 2 rectal neuroendocrine tumors have a nonnegligible rate of lymph node metastasis. Local excision is a feasible choice for tumors ≤ 1.5 cm without metastasis, while radical resection is more beneficial in those > 1.5 cm. See Video Abstract.
Ceftaroline for Central Nervous System Infections: Case Report of a Young Infant, and Scoping Review
Authors: Urbach Haley , Sileo Nicole , Lerma Sergio , Nguyen Kevin , Sosa Soto Giordano , Nielsen Marisa , Heiderich Amy , Holsapple James , Vuppula Sharon , Campbell Jeffrey I.
Published: March 2024

Background:

Managing health care acquired and device-associated intracranial infections in young children can be challenging given adverse antibiotic side effects and difficulties in achieving adequate central nervous system (CNS) antibiotic concentrations. Ceftaroline is a cephalosporin with a favorable safety profile and activity against methicillin-resistant Staphylococci and several Gram-negative organisms. Published data on the use of ceftaroline for CNS infections in children and adults are limited.

Methods:

We describe a 2-month-old infant with ventriculo-subgaleal shunt-associated methicillin-resistant Staphylococcus epidermidis ventriculitis, which was successfully treated with ceftaroline, in addition to vancomycin and rifampin. We conducted a scoping review of English-language literature retrieved from PubMed, EMBASE and Web of Science that assessed the use of ceftaroline for CNS infections.

Results:

We identified 22 articles for inclusion in our review, which described 92 unique patients, of whom 2 were <21 years old. Ceftaroline was commonly used in conjunction with other antibiotics to treat infections caused by Staphylococcus aureus, coagulase-negative Staphylococci and Streptococcus pneumoniae. Most case reports described clinical success with ceftaroline, though small case series and cohort studies yielded mixed efficacy assessments. Adverse effects attributed to ceftaroline were rare and included reversible myelosuppression, eosinophilia, hepatotoxicity and nephrotoxicity. Pharmacokinetic/pharmacodynamic studies suggested similar CNS penetration through inflamed meninges as other beta lactam antibiotics.

Conclusions:

We identified a growing body of published evidence supporting the use of ceftaroline in combination with other agents for the treatment of CNS infections. In absence of clinical trials, additional real-world data are needed to define the efficacy and safety of ceftaroline for children and adults with CNS infections.
Joint Fluid Cell Count in Acute Bacterial Arthritis Patients Proven Positive Culture in Children
Authors: Otsubo Yuto , Shibata Meiwa , Hataya Hiroshi , Ota Norikazu , Horikoshi Yuho
Published: March 2024

Background:

Acute bacterial arthritis (ABA) is a serious, pediatric infection that can result in motor comorbidities. Normally, a joint fluid white blood cell (WBC) count of 50,000 or more cells/mm3 is used to make a presumptive diagnosis of ABA. This study evaluated the utility of the joint fluid WBC count for diagnosing pediatric ABA confirmed by a positive culture result.

Methods:

Patients with ABA between March 2010 and March 2023 at Tokyo Metropolitan Children’s Medical Center were included. ABA was confirmed by positive joint fluid culture results for a pathogenic organism. Patients with negative results and those without a joint fluid WBC count were excluded. Electronic medical records were retrospectively reviewed for demographic data, timing of arthrocentesis, culture results and the joint fluid WBC count.

Results:

Ninety-five patients with ABA were identified; of these, 22 were included. The median age was 5 years [interquartile range (IQR): 2–10 years]. Males comprised 55% of the population. The median joint fluid WBC count was 19,575 (IQR: 6806–47,388) cells/mm3, and 23% of the patients had 50,000 cells/mm3 or more. The median time from symptom onset to arthrocentesis was 3 days (IQR: 2–5 days). The isolated organisms were methicillin-susceptible Staphylococcus aureus (50%), methicillin-resistant S. aureus (9%), Streptococcus pyogenes (27%), Streptococcus pneumoniae (5%), Klebsiella pneumoniae (5%) and Salmonella spp. (5%).

Conclusions:

Most of the patients with ABA confirmed by positive results of a joint fluid culture had a joint fluid WBC count of less than 50,000 cells/mm3.
Acute Flaccid Myelitis With Human Rhinovirus A19 Detection: Case Report and Literature Review
Authors: Murayama Yurie , Aizawa Yuta , Ikuse Tatsuki , Izumita Ryohei , Nukaga Shunsuke , Kaneko Masahiro , Yamada Takeshi , Ono Takeshi , Matsui Ko , Suda Masashi , Saitoh Akihiko
Published: March 2024

Human rhinovirus (HRV) has been sporadically detected in patients with acute flaccid myelitis (AFM). We report a case of AFM in a 2-year-old boy with severe neurologic sequelae, whose nasopharyngeal and stool samples tested positive for HRV-A19. Clinical information related to AFM with HRV is limited. Further study of the association of AFM with HRV is warranted.
Defining suffering in pain. A systematic review on pain-related suffering using natural language processing
Authors: Noe-Steinmüller Niklas , Scherbakov Dmitry , Zhuravlyova Alexandra , Wager Tor D. , Goldstein Pavel , Tesarz Jonas
Published: March 2024

Understanding, measuring, and mitigating pain-related suffering is a key challenge for both clinical care and pain research. However, there is no consensus on what exactly the concept of pain-related suffering includes, and it is often not precisely operationalized in empirical studies. Here, we (1) systematically review the conceptualization of pain-related suffering in the existing literature, (2) develop a definition and a conceptual framework, and (3) use machine learning to cross-validate the results. We identified 111 articles in a systematic search of Web of Science, PubMed, PsychINFO, and PhilPapers for peer-reviewed articles containing conceptual contributions about the experience of pain-related suffering. We developed a new procedure for extracting and synthesizing study information based on the cross-validation of qualitative analysis with an artificial intelligence–based approach grounded in large language models and topic modeling. We derived a definition from the literature that is representative of current theoretical views and describes pain-related suffering as a severely negative, complex, and dynamic experience in response to a perceived threat to an individual's integrity as a self and identity as a person. We also offer a conceptual framework of pain-related suffering distinguishing 8 dimensions: social, physical, personal, spiritual, existential, cultural, cognitive, and affective. Our data show that pain-related suffering is a multidimensional phenomenon that is closely related to but distinct from pain itself. The present analysis provides a roadmap for further theoretical and empirical development.
MicroRNA let-7b enhances spinal cord nociceptive synaptic transmission and induces acute and persistent pain through neuronal and microglial signaling
Authors: Chen Ouyang , Jiang Changyu , Berta Temugin , Powell Gray Bethany , Furutani Kenta , Sullenger Bruce A. , Ji Ru-Rong
Published: March 2024

Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced short-term (<24 hours) mechanical allodynia and heat hyperalgesia, a response that is compromised in Tlr7

−/−
or Trpa1

−/−
mice. Ex vivo and in vivo calcium imaging in GCaMP6-report mice revealed increased calcium signal in spinal cord afferent terminals and doral root ganglion/dorsal root ganglia neurons following spinal perfusion and intraplantar injection of let-7b. Patch-clamp recordings also demonstrated enhanced excitatory synaptic transmission (miniature excitatory postsynaptic currents [EPSCs]) in spinal nociceptive neurons following let-7b perfusion or optogenetic activation of axonal terminals. The elevation in spinal calcium signaling and EPSCs was dependent on the presence of toll-like receptor-7 (TLR7) and transient receptor potential ion channel subtype A1 (TRPA1). In addition, endogenous let-7b is enriched in spinal cord synaptosome, and peripheral inflammation increased let-7b in doral root ganglion/dorsal root ganglia neurons, spinal cord tissue, and the cerebrospinal fluid. Notably, let-7b antagomir inhibited inflammatory pain and inflammation-induced synaptic plasticity (EPSC increase), suggesting an endogenous role of let-7b in regulating pain and synaptic transmission. Furthermore, intrathecal injection of let-7b, at a higher dose (10 μg), induced persistent mechanical allodynia for >2 weeks, which was abolished in Tlr7

−/−
mice. The high dose of let-7b also induced microgliosis in the spinal cord. Of interest, intrathecal minocycline only inhibited let-7b–induced mechanical allodynia in male but not female mice. Our findings indicate that the secreted microRNA let-7b has the capacity to provoke pain through both neuronal and glial signaling, thereby establishing miRNA as an emerging neuromodulator.
Body constitutions of traditional Chinese medicine caused a significant effect on irritable bowel syndrome
Authors: Liao Kuo-Fan , Tsai Han-Ying , Chen Cheng-Fong , Hsu Teh-Fu , Hsu Chun-Yi , Ho Ta-Kai , Liu Ding-Hao , Kao Chung-Lan , Wang Chien-Ying , Hsieh Ai-Ru
Published: March 2024

Background:

According to the theory of traditional Chinese medicine (TCM), all types of body constitutions, except for the Gentleness (ie, the control group in our study), have disease susceptibility and affect the disease development process. This study attempted to investigate the relationship between TCM body constitutions and irritable bowel syndrome (IBS).

Methods:

This cross-sectional study was based on Taiwan Biobank (TWB) and collected clinical data from 13 941 subjects aged 30 to 70. The results of the study showed that subjects with Yang-deficiency (N = 3161 subjects, odds ratio [OR] = 2.654, 95% CI = 1.740-3.910), Ying-deficiency (N = 3331 subjects, OR = 1.096, 95% CI = 0.627-1.782) or Stasis (N = 2335 subjects, OR = 1.680, 95% CI = 0.654-3.520) were more likely to have IBS.

Results:

If the subjects with two or more TCM body constitutions: Yang-deficiency + Ying-deficiency (OR = 3.948, 95% CI = 2.742–5.560), Yang-deficiency + Stasis (OR = 2.312, 95% CI = 1.170-4.112), Ying-deficiency + Stasis (OR = 1.851, 95% CI = 0.828-3.567), or Yang-deficiency + Ying-deficiency + Stasis (OR = 3.826, 95% CI = 2.954-4.932) were also prone to IBS.

Conclusion:

These results confirmed the high correlation between TCM body constitutions and IBS. Because the current treatment for IBS is not entirely satisfactory, integrated traditional Chinese and Western medicine might provide patients with an alternative treatment option to alleviate IBS.
Impact of hyperuricemia on 5-year clinical outcomes in patients with critical limb ischemia following percutaneous transluminal angioplasty
Authors: An Seong Joon , Ahn Woo Jin , Rha Seung-Woon , Park Soohyung , Hyun Su Jin , Cha Jin Ah , Byun Jae Kyeong , Choi Se Yeon , Choi Cheol Ung , Oh Dong Joo , Choi Byoung Geol
Published: March 2024

Background

A growing evidence on the correlation between hyperuricemia and cardiovascular disease (CVD) has been previously reported. However, there have been limited data on the impact of hyperuricemia on long-term clinical outcomes in patients with critical limb ischemia (CLI) who underwent percutaneous transluminal angioplasty (PTA).

Methods

A total of 425 peripheral artery disease patients who underwent PTA for CLI were enrolled. The patients were divided into the hyperuricemia group (n = 101) and the normal group (n = 324). The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction, any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was a major adverse limb event (MALE), including any repeated PTA, and target extremity surgery. Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust for potential confounders.

Results

After IPTW matching analysis, compared to the normal group, the hyperuricemia group was associated with a higher incidence of MACCE (20.7% vs. 13.6%, hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.15–2.38, P = 0.006) including non-cardiac death (11.7% vs. 6.3%, HR: 1.95, 95% CI: 1.19–3.19, P = 0.006) and MALE (47.7% vs. 36.0%, HR: 1.62, 95% CI: 1.23–2.13, P = 0.001) including non-target extremity revascularization (15.0% vs. 6.8%, HR: 2.42, 95% CI: 1.52–3.84, P < 0.001).

Conclusion

In the present study, hyperuricemia was associated with worse clinical outcomes in patients with CLI following PTA during 5-year clinical follow-up. Efficacy of controlling hyperuricemia in improving clinical outcomes should be evaluated in further studies.
De novo lipid synthesis and polarized prenylation drives cell invasion through basement membrane
Authors: Park Kieop , Garde Aastha , Thendral Siddharthan B. , Soh Adam W. J. , Chi Qiuyi , Sherwood David R.
Published: March 2024

Invasive cells form large, specialized protrusions to break through basement membrane (BM) matrix barriers. Park et al., reveal a crucial requirement for de novo lipid synthesis and a dynamic polarizing prenylation system to rapidly construct invasive protrusions that breach BMs.

To breach basement membrane (BM), cells in development and cancer use large, transient, specialized lipid-rich membrane protrusions. Using live imaging, endogenous protein tagging, and cell-specific RNAi duringC. elegansanchor cell (AC) invasion, we demonstrate that the lipogenic SREBP transcription factor SBP-1 drives expression of the fatty acid synthesis enzymes POD-2 and FASN-1 prior to invasion. We show that phospholipid producing LPIN-1 and sphingomyelin synthase SMS-1, which use fatty acids as substrates, produce lysosome stores that build the AC’s invasive protrusion, and that SMS-1 also promotes protrusion localization of the lipid raft partitioning ZMP-1 matrix metalloproteinase. Finally, we discover that the endoplasmic reticulum (ER)-associated HMG-CoA reductase HMGR-1, which generates isoprenoids for prenylation, enriches at the AC invasive front, and that the final ER prenylation enzyme, ICMT-1, localizes to ER exit sites that dynamically polarize to deliver prenylated GTPases for protrusion formation. Together, these results reveal a collaboration between lipogenesis and a polarized lipid prenylation system that drives invasive protrusion formation.
In-cell structure and snapshots ofcopiaretrotransposons in intact tissue by cryo-electron tomography
Authors: Klumpe Sven , Senti Kirsten A. , Beck Florian , Sachweh Jenny , Hampoelz Bernhard , Ronchi Paolo , Yeroslaviz Assa , Briggs John A.G. , Brennecke Julius , Beck Martin , Plitzko Jürgen M.
Published: March 2024

Long terminal repeat (LTR) retrotransposons belong to the transposable elements (TE), autonomously replicating genetic elements that integrate into the host’s genome. LTR retrotransposons represent a major component of genomes across the tree of life; some derived sequences have even been domesticated by the host to perform cellular functions in essential processes such as development. Among animals,Drosophila melanogasterserves as an important model organism for TE research, harboring several LTR retrotransposons, including the Ty1-copiafamily, which is evolutionarily related to retroviruses and forms virus-like particles (VLPs). The architectural organization ofcopiaVLPsin situhas remained unknown. In this study, we use cryo-FIB milling and lift-out approaches to visualizecopiaVLPs in isolated ovarian cells and intact egg chambers and resolve thein situ copiacapsid structure to 7.7 Å resolution by cryo-ET. While cytosoliccopiaVLPs vary in size, nuclear VLPs are homogenous and form densely packed clusters, supporting a model in which nuclear import acts as a size selector. By analyzing flies deficient in the TE-suppressing PIWI-piRNA pathway, we observe a change incopialocalization from cytosolic to nuclear during spermatogenesis in testes. Our findings provide insights into the cellular structural biology of an active LTR retrotransposon and shed light on the replication cycle ofcopiain the context of host gametogenesis.
Investigating the Evolution of Green Algae with a Large Transcriptomic Dataset
Authors: Ferranti David A. , Delwiche Charles F.
Published: March 2024

The colonization of land by plants, thought to have occurred approximately 450-500 million years ago (Ma) is one of the most important events in the history of life on Earth. Land plants, hereafter referred to as “embryophytes,” comprise the foundation of every terrestrial biome, making them an essential lineage for the origin and maintenance of biodiversity. The embryophytes form a monophyletic clade within one of the two major phyla of the green algae, the Streptophyta. Estimates from fossil data and molecular clock analyses suggest the charophytes diverged from the other main phylum of green algae, the Chlorophyta, as much as 1500 Ma. Here we present a phylogenetic analysis using transcriptomic and genomic data of 62 green algae and embryophyte operational taxonomic units, 31 of which were assembledde novofor this project. We focus on identifying the charophyte lineage that is sister to embryophytes, and show that the Zygnematophyceae have the strongest support, followed by the Charophyceae. We demonstrate that this phylogenetic tree topology is robust across different phylogenetic models and methods. Furthermore, we examine amino acid and codon usage across the tree and find these data broadly follow the phylogenetic tree. We conclude by searching the dataset for several protein domains and gene families known to be important in embryophytes, including the ethylene signaling pathway and various ion transporters. Many of these domains and genes have homologous sequences in the charophyte lineages, giving insight into the processes that underlay the colonization of the land by plants.
Genetic polymorphisms of Leukocyte Immunoglobulin-Like Receptor B3 (LILRB3) gene in African American kidney transplant recipients are associated with post-transplant graft failure
Authors: Sun Zeguo , Yi Zhengzi , Wei Chengguo , Wang Wenlin , Cravedi Paolo , Tedla Fasika , Ward Stephen C. , Azeloglu Evren , Schrider Daniel R. , Li Yun , Ali Sumaria , Ren Tianyuan , Liu Shun , Liang Deguang , Fu Jia , Liu Tong , Li Hong , Xi Caixia , Vy Thi Ha , Mosoyan Gohar , Sun Quan , Kumar Ashwani , Zhang Zhongyang , Farouk Samira , Campell Kirk , Ochando Jordi , Lee Kyung , Coca Steve , Xiang Jenny , Connolly Patti , Gallon Lorenzo , Colvin Robert , Menon Madhav , Nadkarni Girish , He John C. , Kraft Monica , Jiang Xuejun , Zhang Xuewu , Zhang Weiguo , Chen Shu-hsia , Heeger Peter , Zhang Weijia
Published: March 2024

Background

African American (AA) kidney transplant recipients exhibit a higher rate of graft loss compared to other racial and ethnic populations, highlighting the need to identify causative factors underlying this disparity.

Method

We analyzed RNA sequences of pretransplant whole blood from subjects followed in three kidney transplant cohorts to identify single nucleotide polymorphisms (SNPs) associated with death censored graft loss (DCGL). We employed a meta-analysis to uncover key transcriptional signatures and pathways associated with the identified SNPs and used single cell RNA to define cellular specificity. We characterized SNP functions usingin vitroimmunological and survival assays and tested for associations between the identified SNPs and other immune-related diseases using a ∼30,100 subject, electronic health record (EHR)-linked database.

Results

We uncovered a cluster of four consecutive missense SNPs in the Leukocyte Immunoglobulin-Like Receptor B3 (LILRB3, a negative immune response regulator) gene that strongly associated with DCGL. ThisLILRB3-4SNPs cluster encodes missense mutations at amino acids 617-618 proximal to a SHP-1/2 phosphatase-binding ITIM motif.LILRB3-4SNPs is specifically enriched within subjects of AA ancestry (8.6% prevalence vs 2.3% in Hispanic and 0.1% in European populations), is not linked toAPOL1G1/G2 alleles, and exhibited a strong association with DCGL. Analysis of PBMC and transplant biopsies from recipients withLILRB3-4SNPs showed evidence of enhanced adaptive immune responsiveness and ferroptosis-associated death in monocytes. Overexpression of the variant allele in THP-1 cells (macrophage line) induced augmented inflammation and ferroptosis, which were attenuated by a ferroptosis inhibitor, verifying a causal link. TheLILRB3-4SNPs also associated with multiple systemic and organ-specific immune-related diseases in AAs, consistent with conferring a broadly relevant immune function.

Conclusion

theLILRB3-4SNPs represent a functionally important, distinct genetic risk factor for kidney transplant outcome and development/severity of other immune-related diseases in patients of AA ancestry. Pharmacological targeting of ferroptosis should be tested to prevent or treat these disease processes in AA recipients carryingLILRB3-4SNPs.
Charting is Never Exciting: Measuring Physician Time Use in Medical Dramas
Authors: Jackson Katelin C , Miller Kayla A , Hill Samantha M , Johnson Stephanie S. , Reimanis Laila A. , Lofgren Eric T
Published: March 2024

Objectives

This study aimed to explore the use of medical dramas to train observers when in-person observations or patient contact in clinical settings is impossible. The study also assessed the media’s portrayal of the medical profession and compared time use patterns in medical dramas to previous hospital observational studies.

Design

Activity-pattern observational study using Work Observation by Activity Timing software.

Setting

The hospital, ICU, and community settings of medical television shows.

Participants

The first and last season of the main cast of three medical dramas; Grey’s Anatomy, Scrubs, and ER.

Main outcome measures

Inter-rater reliability scores were used to assess how well medical dramas can be used as a training tool for observers. Proportions of time spent on daily medical tasks were compared to other in-person hospital studies.

Results

Grey’s Anatomy and Scrubs had excellent Intraclass Correlation Coefficients (ICC) scores for a general medical setting, with Grey’s Anatomy ICC scores for Season 1 0.99 (0.97 to 1.0), and Season 16 0.98 (0.90 to 1.0) and Scrubs ICC scores of 0.91 (0.65 to 0.98) for Season 1 and 0.91 (0.55, 0.99) for Season 8. In contrast, ER had an acceptable ICC score of 0.89 (0.59 to 0.98) for Season 1 and 0.81 (0.35 to 0.96) for Season 15 and might be more suitable for studies exploring activity patterns in the Emergency Department. All had p-values of <0.001.

Conclusions

Medical dramas can serve as training tools when clinical observation is limited or impossible, and our methods reflect these shows’ ease of use and flexibility. Additionally, medical dramas can be selected for their similarity to in-person studies. Still, one should be mindful that inaccuracies in the representation of clinical activity patterns are present. However, using medical dramas to train research staff in direct observation is a feasible and reliable method.