bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified Limbal–Conjunctival Autograft Surgical Technique: Long-Term Results of Recurrence and Complications
Authors: Lee Brendon W. H. , Ip Matthew H. , Tat Lien , Chen Helen , Coroneo Minas T. 
Published: July 2023

Purpose:
The aim of this study was to report the recurrence and complication rates of a modified limbal–conjunctival autograft surgical technique for pterygium excision.

Methods:
This was a retrospective, single-surgeon, single-operating environment, consecutive case series of 176 eyes in 163 patients with a biopsy-proven diagnosis of pterygium. All patients underwent excision using a 23-gauge needle to “behead” the pterygium head, followed by a limbal–conjunctival autograft including ∼50% of the palisades of Vogt. Outcomes measured included recurrence, defined as any conjunctival fibrovascular growth, and complication rates. Correlations between preoperative patient characteristics, pterygium morphology, and intraoperative factors (width of corneal extension, conjunctival defect, and graft) with postoperative recurrence were examined using logistic regression models.

Results:
The median age was 59.5 years and 122 eyes (69.3%) had primary pterygium (type I: 17%, II: 37.5%, and III: 45.5%). Kaplan–Meier analysis demonstrated the median pterygium-free follow-up period to be 723 days (range 46–7230 days). Recurrence was observed in 3 eyes of 2 patients (1.7%). No postoperative graft-related complications were observed. Postoperative symptomatology was transient. Age demonstrated a negative correlation with recurrence (odds ratio 0.888, 95% CI, 0.789–0.998, P = 0.046). However, no other correlations with preoperative or intraoperative factors, including whether pterygium was primary or recurrent, were identified (all P > 0.05).

Conclusions:
This modified limbal–conjunctival autograft technique represents an effective alternative that offers a very low recurrence rate and avoids extensive dissection or antimetabolites, with minimal complications and transient postoperative symptomatology, over a long-term follow-up period. This technique is relatively simple and successful for both primary and recurrent pterygia. Future comparative studies with other surgical techniques may determine which are superior.
Clostridioides difficile Infections During the COVID-19 Pandemic
Authors: Kaura Abhimanyu , Stanton Daniel , Villasante-Tezanos Alejandro , Halder Debopriyo , Reynoso David 
Published: July 2023

Objective
To compare rates of prepandemic Clostridioides difficile infection (CDI) during the COVID-19 pandemic and the rates of antibacterial use prepandemic and during the COVID-19 pandemic.

Design
This was a retrospective data review.

Setting
This study was performed at an academic medical center.

Patients
Patients were all adult patients admitted to the hospital between April 1, 2019, and December 31, 2019, who were tested for CDI and admitted in the same time frame in 2020, and who were tested for CDI were included in the study.

Methods
Retrospective data analysis was conducted across 5 hospitals from April 1 to December 31, 2019 (prepandemic), and on the same dates in 2020 during the pandemic. The standardized infection ratio (SIR) for hospital-acquired CDI (HA-CDI) was calculated for both groups. The mean and normal distributions were calculated for all values in both the groups. The 2 groups were compared using unpaired t tests for continuous variables and χ
2 tests for discrete variables.

Results
Thirty-six patients were diagnosed with HA-CDI before the pandemic (2019), and 45 patients during the pandemic (2020). The 2019 HA-CDI SIRs were 0.47 in 2019 and 0.56 in 2020. Days of therapy per 1000 patient-days of antibiotics increased from 337.1 to 364.6 (P = 0.0057). Analysis of 153 inpatients with diarrhea revealed no positive association between COVID and CDI.

Conclusion
During the COVID-19 pandemic, empiric broad-spectrum antibacterial use increased in our system, as did HA-CDI SIR compared with the national standards. We did not observe a positive correlation between COVID-19 and CDI.
Computed Tomography and Magnetic Resonance Imaging Signs of Chronic Liver Rejection: A Case-Control Study
Authors: Asmundo Luigi , Rizzetto Francesco , Sgrazzutti Cristiano , Carbonaro Luca A. , Mazzarelli Chiara , Centonze Leonardo , Rutanni Davide , De Carlis Luciano , Vanzulli Angelo 
Published: July 2023

Objective
In liver transplantation, chronic rejection is still poorly studied. This study aimed to investigate the role of imaging in its recognition.

Methods
This study is a retrospective observational case-control series. Patients with histologic diagnosis of chronic liver transplant rejection were selected; the last imaging examination (computed tomography or magnetic resonance imaging) before the diagnosis was evaluated. At least 3 controls were selected for each case; radiological signs indicative of altered liver function were analyzed. χ2 Test with Yates correction was used to compare the rates of radiologic signs in the case and control groups, also considering whether patients suffered chronic rejection within or after 12 months. Statistical significance was set at P < 0.050.

Results
A total of 118 patients were included in the study (27 in the case group and 91 in the control group). Periportal edema was appreciable in 19 of 27 cases (70%) and in 6 of 91 controls (4%) (P < 0.001); ascites and hepatomegaly were present in 14 of 27 cases (52%) and 12 of 27 cases (44%), respectively, and in 1 of 91 controls (1%) (P < 0.001); splenomegaly was present in 13 of 27 cases (48%) and in 8 of 91 controls (10%) (P < 0.001); and biliary tract dilatation was present in 13 of 27 cases (48%) and in 11 of 91 patients controls (5%) (P < 0.001). In the controls, periportal edema was significantly less frequent beyond 12 months after transplant (1% vs 11%; P = 0.020); the other signs after 12 months were not significant.

Conclusions
The identification of periportal edema, biliary dilatation, ascites, and hepatosplenomegaly can serve as potential warning signs of ongoing chronic liver rejection. It is especially important to investigate periportal edema if it is present 1 year or more after orthotopic liver transplantation.
Modelling the Effect of Allopregnanolone on the Resolution of Spike-Wave Discharges
Authors: Ahmed Maliha , Campbell Sue Ann 
Published: July 2023

AbstractObjectiveChildhood absence epilepsy (CAE) is a paediatric generalized epilepsy disorder with a confounding feature of resolving in adolescence in a majority of cases. In this study, we modelled how the small-scale (synapse-level) effect of progesterone metabolite allopregnanolone induces a large-scale (network-level) effect on a thalamocortical circuit associated with this disorder. In particular, our goal was to understand the role of sex steroid hormones in the spontaneous remission of CAE.MethodsThe conductance-based computational model consisted of single-compartment cortical pyramidal, cortical interneurons, thalamic reticular and thalamocortical relay neurons, each described by a set of ordinary differential equations. Excitatory and inhibitory synapses were mediated by AMPA, GABAa and GABAb receptors. The model was implemented using the NetPyne modelling tool and the NEURON simulator.ResultsThe action of allopregnanolone on individual GABAa-receptor mediated synapses has an ameliorating effect on spike-wave discharges (SWDs) associated with absence seizures. This effect is region-specific and most significant in the thalamus, particularly the synapses between thalamic reticular neurons.SignificanceThe remedying effect of allopregnanolone on SWDs may possibly be true only for individuals that are predisposed to remission due to intrinsic connectivity differences or differences in tonic inhibition. These results are a useful first-step and prescribe directions for further investigation into the role of ALLO together with these differences to distinguish between models for CAE-remitting and non-remitting individuals.
Integrative spatial analysis reveals a multi-layered organization of glioblastoma
Authors: Greenwald Alissa C. , Darnell Noam Galili , Hoefflin Rouven , Simkin Dor , Gonzalez-Castro L. Nicolas , Mount Christopher , Hirsch Dana , Nomura Masashi , Talpir Tom , Kedmi Merav , Goliand Inna , Medici Gioele , Li Baoguo , Keren-Shaul Hadas , Weller Michael , Addadi Yoseph , Neidert Marian C. , Suvá Mario L. , Tirosh Itay 
Published: July 2023

SummaryGlioma contains malignant cells in diverse states. Hypoxic regions are associated with a unique histology of pseudopalisading cells, while other regions appear to have limited histological organization, reflecting the diffuse nature of glioma cells. Here, we combine spatial transcriptomics with spatial proteomics and novel computational approaches to define glioma cellular states at high granularity and uncover their organization. We find three prominent modes of cellular organization. First, cells in any given state tend to be spatially clustered, such that tumors are composed of small local environments that are each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. Despite the unique composition of each tumor, this pairing of states remains largely consistent across tumors. Third, the pairwise interactions that we detect collectively define a global architecture composed of five layers. Hypoxia appears to drive this 5-layered organization, as it is both associated with unique states of surrounding cells and with a long-range organization that extends from the hypoxic core to the infiltrative edge of the tumor. Accordingly, tumor regions distant from any hypoxic foci and tumors that lack hypoxia such as IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of gliomas at the resolution of cellular states and highlight the role of hypoxia as a long-range tissue organizer.
Multimodal imaging for validation and optimization of ion channel-based chemogenetics in nonhuman primates
Authors: Hori Yuki , Nagai Yuji , Hori Yukiko , Oyama Kei , Mimura Koki , Hirabayashi Toshiyuki , Inoue Ken-ichi , Fujinaga Masayuki , Zhang Ming-Rong , Takada Masahiko , Higuchi Makoto , Minamimoto Takafumi 
Published: July 2023

AbstractChemogenetic tools provide an opportunity to manipulate neuronal activity and behavior selectively and repeatedly in nonhuman primates (NHPs) with minimal invasiveness. Designer Receptors Exclusively Activated by Designer Drugs are one example that is based on mutated muscarinic acetylcholine receptors. Another channel-based chemogenetic system available for neuronal modulation in NHPs uses Pharmacologically Selective Actuator Modules (PSAMs), which are selectively activated by Pharmacologically Selective Effector Molecules (PSEMs). To facilitate the use of the PSAM/PSEM system, the selection and dosage of PSEMs should be validated and optimized for NHPs. To this end, we used a multimodal imaging approach. We virally expressed excitatory PSAM (PSAM4-5HT3) in the striatum and the primary motor cortex of two macaque monkeys, and visualized its location through positron emission tomography (PET) with the reporter ligand [18F]ASEM. Chemogenetic excitability of neurons triggered by two PSEMs (uPSEM817 and uPSEM792) was evaluated using [18F]fluorodeoxyglucose-PET imaging, with uPSEM817 being more efficient than uPSEM792. Pharmacological magnetic resonance imaging showed that increased brain activity in the PSAM4-expressing region began approximately 13 min after uPSEM817 administration and continued for at least 60 min. Our multimodal imaging data provide valuable information regarding the manipulation of neuronal activity using the PSAM/PSEM system in NHPs, facilitating future applications.Significance statementLike other chemogenetic tools, the ion channel-based system called Pharmacologically Selective Actuator Module/Pharmacologically Selective Effector Molecule (PSAM/PSEM) allows remote manipulation of neuronal activity and behavior in living animals. Nevertheless, its application in non-human primates (NHPs) is still limited. Here, we used multi-tracer positron emission tomography (PET) imaging and pharmacological magnetic resonance imaging (MRI) to visualize an excitatory chemogenetic ion channel (PSAM4-5HT3) and validate its chemometric function in macaque monkeys. Our results provide the optimal agonist, dose, and timing for chemogenetic neuronal manipulation, facilitating the use of the PSAM/PSEM system and expanding the flexibility and reliability of circuit manipulation in NHPs in a variety of situations.
Deviance detection in subthalamic neural population responses to natural stimuli in bats
Authors: Wetekam Johannes , Hechavarría Julio , López-Jury Luciana , González-Palomares Eugenia , Kössl Manfred 
Published: July 2023

AbstractDeviance detection describes an increase of neural response strength caused by a stimulus with a low probability of occurrence. This ubiquitous phenomenon has been reported for multiple species, from subthalamic areas to auditory cortex. While cortical deviance detection has been well characterised by a range of studies covering neural activity at population level (mismatch negativity, MMN) as well as at cellular level (stimulus-specific adaptation, SSA), subcortical deviance detection has been studied mainly on cellular level in the form of SSA. Here, we aim to bridge this gap by using noninvasively recorded auditory brainstem responses (ABRs) to investigate deviance detection at population level in the lower stations of the auditory system of a hearing specialist: the batCarollia perspicillata. Our present approach uses behaviourally relevant vocalisation stimuli that are closer to the animals’ natural soundscape than artificial stimuli used in previous studies that focussed on subcortical areas. We show that deviance detection in ABRs is significantly stronger for echolocation pulses than for social communication calls or artificial sounds, indicating that subthalamic deviance detection depends on the behavioural meaning of a stimulus. Additionally, complex physical sound features like frequency- and amplitude-modulation affected the strength of deviance detection in the ABR. In summary, our results suggest that at population level, the bat brain can detect different types of deviants already in the brainstem. This shows that subthalamic brain structures exhibit more advanced forms of deviance detection than previously known.
Mass2SMILES: deep learning based fast prediction of structures and functional groups directly from high-resolution MS/MS spectra
Authors: Elser David , Huber Florian , Gaquerel Emmanuel 
Published: July 2023

AbstractModern mass spectrometry-based metabolomics generates vast amounts of mass spectral data as part of the chemical inventory of biospecimens. Annotation of the resulting MS/MS spectra remains a challenging task that mostly relies on database interrogations,in silicoprediction and interpretation of diagnostic fragmentation schemes and/or expert knowledge-based manual interpretations. A key limitation is additionally that these approaches typically leave a vast proportion of the (bio)chemical space unannotated. Here we report a deep neural network method to predict chemical structures solely from high-resolution MS/MS spectra. This novel approach initially relies on the encoding of SMILES strings from chemical structures using a continuous chemical descriptor space that had been previously implemented for molecule design. The deep neural network was trained on 83,358 natural product-derived MS/MS spectra of the GNPS library and of the NIST HRMS database with addition of the calculated neutral losses for those spectra. After this training and parameter optimization phase, the deep neural network approach was then used to predict structures from MS/MS spectra not included in the training data-set. Our current version, implemented in the Python programming language, accurately predicted 7 structures from 744 validation structures and the following 14 structures had aTanimotosimilarity score above 0.9 when compared to the true structure. It was also able to correctly identify two structures from the CASMI 2022 international contest. On average theTanimotosimilarity is of 0.40 for data of the CASMI 2022 international contest and of 0.39 for the validation data-set. Finally, our deep neural network is also able to predict the number of 60 functional groups as well as the molecular formula of chemical structures and adduct type for the analyzed MS/MS spectra. Importantly, this deep neural network approach is extremely fast, in comparison to currently available methods, making it suitable to predict on regular computers structures for all substances within large metabolomics datasets.
Increasing Chemotherapeutic Efficacy Using pH Modulating and Doxorubicin Releasing Injectable Chitosan-Polyethylene Glycol Hydrogels
Authors: Ahmed Zahra , LoGiudice Kevin , Mays Gavin , Schorr Angelina , Rowey Rachel , Yang Haisong , Trivedi Shruti , Srivastava Vikas 
Published: July 2023

AbstractModulation of pH is crucial to maintaining the chemical homeostasis of biological environments. The irregular metabolic pathways exhibited by cancer cells result in the production of acidic byproducts that are excreted and accumulate in the extracellular tumor microenvironment, reducing its pH. As a consequence of the lower pH in tumors, cancer cells increase the expression of metastatic phenotypes and chemotherapeutic resistance. A significant limitation in current cancer therapies is the inability to locally deliver the chemotherapy, leading to significant damage to healthy cells in systemic administration. To overcome these challenges, we present an injectable chitosan-polyethylene glycol hydrogel that is dual-loaded with doxorubicin and sodium bicarbonate providing alkaline buffering of extracellular acidity and simultaneous chemotherapeutic delivery to increase chemotherapeutic efficacy. We conducted in vitro studies of weak base chemotherapeutic and alkaline buffer release from the hydrogel. The release of doxorubicin from hydrogels increased in a low pH environment and was dependent on the encapsulated sodium bicarbonate concentration. We investigated the influence of pH on doxorubicin efficacy and viability of MCF-7 and MDA-MB-231 breast cancer cell lines. The results show a 2 to 3 fold increase in IC50values from neutral pH to low pH, showing decreased cancer cell viability at neutral pH as compared to acidic pH. The IC50results were shown to correlate with a decrease in intracellular uptake of doxorubicin at low pH. The proposed hydrogels were confirmed to be non-toxic to healthy MCF-10A mammary epithelial cells. Rheological studies were performed to verify that the dual loaded hydrogels were injectable. The mechanical and release properties of the hydrogels were maintained after extended storage. The chemotherapeutic activity of doxorubicin was evaluated in the presence of the proposed pH regulating hydrogels. The findings suggest a promising non-toxic, biodegradable hydrogel buffer delivery system that can achieve two simultaneous important goals of local acidosis neutralization and chemotherapeutic release.
National seroprevalence and risk factors of bluetongue virus in domestic ruminants in Peru
Authors: Navarro-Mamani Dennis A. , Jurado Pucllas Jessica , Vargas-Calla Ana , Ponce Dextre Kevin , Zarate Quispe Yari , Murga-Moreno César A. , Ibelice Perez C , Ruben Villacaqui A , Miguel Ara G , Incil Edith , Pedro Ortiz O , Gerónimo Hermelinda Rivera 
Published: July 2023

AbstractBluetongue virus (BTV) is a global infection primarily transmitted among domestic and wild ruminant populations throughCulicoidesspp. midges. Infection is highly prevalent across temperate and tropical regions; however, significant changes in the global distribution of BTV have been observed in recent years. We aimed to evaluate the national BTV seroprevalence and its risk factors among domestic ruminants (cattle, sheep and goats) in Peru. Ruminant sera (cattle= 3 452, sheep= 2 786 and goats=1 568) were collected using a random, two-stage clustering method and analyzed by c-ELISA. The national BTV seroprevalence was 12.7% (95% CI: 11.00-14.63%) and the seropositivity rate for each species was 19.29% (95% CI: 16.0%–31.1%) in cattle, 8.4 (95% CI: 6.6%–10.5%) in sheep, and 9.2% (95% CI: 5.6%–14.8%) in goats. Bivariate and multiple logistic regression analysis were used to evaluate risk factors for BTV seropositivity and to estimate Odds Ratios (OR) with 95% CI. We found that age, altitude, and maximum temperature were identified as crucial factors influencing the prevalence of BTV seroprevalence in cattle, sheep and goats. Older animals, particularly cattle and goats between 6 and 24 months and above 24 months, exhibited a significantly higher likelihood of BTV infection. Additionally, higher altitudes above 3000 masl played a protective role, reducing the risk of BTV transmission. Furthermore, increased maximum temperatures, especially exceeding 30 °C, were associated with a greater prevalence of BTV. This study lays the groundwork for identifying BTV serotypes andCulicoidesspp. in different regions, including altitudes above 3000 masl, to enhance BTV surveillance in Peru.
Unsuspected consequences of synonymous and missense variants inOCA2can be detected in blood cell RNA samples of patients with albinism
Authors: Michaud Vincent , Sequeira Angèle , Mercier Elina , Lasseaux Eulalie , Plaisant Claudio , Hadj-Rabia Smail , Whalen Sandra , Bonneau Dominique , Dieux-Coeslier Anne , Morice-Picard Fanny , Coursimault Juliette , Arveiler Benoît , Javerzat Sophie 
Published: July 2023

ABSTRACTOculocutaneous albinism type 2 (OCA2) is the second most frequent form of albinism and represents about 30% of OCA worldwide. As with all types of OCA, patients present with hypopigmentation of hair and skin as well as severe visual abnormalities. We focused on a subgroup of 29 patients for whom genetic diagnosis was pending because at least one of their identified variants in or around exon 10 ofOCA2is of uncertain significance (VUS). By minigene assay, we investigated the effect of these VUS on exon 10 skipping and showed that not only intronic but also some synonymous variants can result in enhanced exon skipping. We further found that excessive skipping of exon 10 could be detected directly on blood samples of patients and of their one parent with the causal variant, avoiding invasive skin biopsies. Moreover, we show that variants which result in lack of detectableOCA2mRNA can be identified from blood samples as well, as shown for the most commonOCA2pathogenic missense variant c.1327G>A/p.(Val443Ile). In conclusion, blood cell RNA analysis allows testing the potential effect of anyOCA2VUS on transcription products. This should help to elucidate yet unsolved OCA2 patients and improve genetic counseling.SIGNIFICANCEOur study allows us to reconsider variants of unknown significance ofOCA2as pathogenic as they induce exon 10 skipping. We show that mis-splicing as well as other types of transcripts imbalance can be detected directly from blood cell samples, avoiding invasive biopsies. We recommend systematic collection of a blood RNA sample from patients with inconclusive genetic diagnosis and suspected OCA2 (e.g., only one pathogenic variant inOCA2; 1 VUS; 2 VUS intrans).