bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic analysis reveals dysregulation of peripheral blood neutrophils in patients with Multiple Sclerosis
Authors: Smith Katie J , Lim Zachary , Vermeren Sonja , Miron Veronique E , Dimeloe Sarah , Davidson Donald J , Williams Anna , Gwyer Findlay Emily
Published: January 2025

Introduction

Multiple Sclerosis (MS) is a complex auto-inflammatory disease affecting the brain and spinal cord, which results in axonal de-myelination and symptoms including fatigue, pain, and difficulties with vision and mobility. The involvement of the immune system in the pathology of MS is well established, particularly the adaptive T cell response, and there has been a particular focus on the IL-17-producing subset of Th17 cells and their role in driving disease. However, the importance of innate immune cells has not been so well characterised.

Method

Here we focused on neutrophils, which are innate immune cells and rapid responders to inflammation, and which have recently been linked to other chronic autoimmune conditions. Multiple strands of evidence in patients with MS and in mice with the experimental autoimmune encephalomyelitis MS model suggest neutrophils may play a role in driving MS inflammation. Here, we performed proteomic analysis on neutrophils from patients with MS and healthy donors, revealing striking differences.

Results

In particular, granule proteins were significantly more abundant in the MS neutrophils compared to the healthy controls, with a particular over-abundance of proteins in primary and secondary granules. In addition, members of the MAVS signalling pathway were differently regulated compared to healthy donor cells.

Conclusion

Finally, we find that MS neutrophils do not suppress T cell activation equivalently to healthy neutrophils, and in particular are unable to suppress expression of CD161 on the T cells, indicative of a suppression of Th17 differentiation. We propose that neutrophil dysregulation in MS may contribute to dysfunctional T cell responses.
Electric heating system for iso-C5 dehydrogenation in the presence of H2S
Authors: Suganuma Hiroyasu , Watanabe Ryo , Verma Priyanka , Akama Hiroshi , Fukuhara Choji
Published: January 2025

This study investigated the effects of an e-reaction system on iso-C5 dehydrogenation. In this system, current is passed through a honeycomb-type catalyst, and the reaction field is heated by the resistance of the substrate. Compared with conventional dehydrogenation via external heating, e-Reaction suppresses side reactions such as thermal decomposition and selectively promotes dehydrogenation. Furthermore, shortening the substrate length enhanced the selectivity of C5-olefins.
An improved growing season index including the maximum temperature and precipitation to predict foliar phenology of alpine grasslands on the Qinghai–Tibetan Plateau
Authors: Sun Qingling , Zhu Jiang , Zhu Siyu , Li Baolin , Zhu Jie , Chen Xiuzhi , Yuan Wenping
Published: January 2025

Phenological model is a useful tool to predict vegetation phenology and investigate the relationship between vegetation and climate. However, compared with temperate and boreal ecosystems, phenological modeling work in alpine regions has received much less attention. In this study, we established a semi-mechanistic phenological model, the AGSI model, considering different impacts of daily maximum and minimum air temperatures and constraints of precipitation and photoperiod for predicting foliar phenology of alpine grasslands on the Qinghai–Tibetan Plateau (QTP). The model was driven by daily minimum temperature (Tmin), daily maximum temperature (Tmax), precipitation averaged over the previous month (PA), and daily photoperiod (Photo). Based on the AGSI model, we further assessed impacts of Tmin, Tmax, PA, and Photo on modeling accuracy, and identified the predominant climatic controls over entire alpine grasslands on the QTP. Results showed that the AGSI model had higher accuracy than other GSI models. Total RMSE of predicted leaf onset and offset dates when evaluated using ground observations was 12.9 d, which decreased those of other models by 10.9%–54.1%. Total modeling accuracy of leaf onset and offset dates was improved by 20.2% after considering the effects of Tmax and PA in the AGSI. Overall, PA and Tmin showed more critical and extensive constraints on foliar phenology of alpine grasslands. The limiting effect of Tmax was also considerable, primarily during July–November. This study provides a simple and effective tool to predict foliar phenology of alpine grasslands and evaluate the climatic effects on vegetation phenological development in alpine regions.
Heavy medicine: the need for ethical stewardship of metal and metalloid-based medicines and technologies
Authors: Day Patrick
Published: January 2025

Metals and metalloids including cobalt, gadolinium, lutetium, and germanium are used in numerous medical applications spanning diverse specialities including orthopedics, radiology, oncology, and healthcare artificial intelligence. These medical advances include cobalt containing orthopedic implants, gadolinium-based contrast agents, lutetium-containing cancer drugs, and germanium-based semiconductors. While these metal and metalloid-based solutions do improve patient care, there is a heavy side to how the elements needed for these solutions are mined, extracted, and discarded. These practices often exploit and harm vulnerable populations and environments. As healthcare professionals, we should be aware of the entire mineral to medicine lifecycle. As providers and consumers of these metal and metalloid-based solutions, we must advocate for more responsible and ethical extraction and recycling practices. As researchers and educators, we must promote and support continued research and development into less resource-intense medical solutions that can both improve patient care and sustainability.
Nomogram for predicting proliferative lupus nephritis in patients with low-level proteinuria
Authors: Lu Yuewen , Tang Ruihan , Tan Li , Xiang Wang , Fan Yuting , Yu Jianwen , Wang Xin , Ye Hongjian , Zhong Zhong , Wu Haishan , Xia Xi , Chen Wei
Published: January 2025

Objectives

Proliferative LN is not uncommon in individuals with proteinuria <0.5 g/24 h, highlighting the importance of predicting proliferative nephritis for effective clinical management. We aimed to develop a predictive model for proliferative LN in this population.

Methods

The enrolled 671 biopsy-proven LN patients were divided into low-level proteinuria (<0.5 g/24 h) and high-level proteinuria (≥0.5 g/24 h) groups. The clinical features, pathological characteristics and long-term outcomes of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to construct a predictive nomogram for proliferative nephritis in low-level proteinuria patients and internal validation was performed using bootstrap-resampling.

Results

One hundred and three of 671 (15.4%) LN patients had low-level proteinuria, 43 (41.7%) of whom showed proliferative LN; the Activity Index and Chronicity Index were 5 [interquartile range (IQR) (4, 7)] and 3 [IQR (2, 4)], respectively. The long-term adverse renal events-free survival was preferable in the low-level proteinuria group. The LASSO-logistic regression identified that age, sex, mean arterial pressure, haemoglobin, platelet, 24-h proteinuria and anti-dsDNA antibodies positivity were associated with proliferative nephritis in those with low-level proteinuria. The predictive model showed an area under curve of 0.900 (95% CI 0.840–0.960) and a bootstrapped result of 0.894 (95% CI 0.832–0.965), with good calibration.

Conclusion

Some 41.7% of the patients with low-level proteinuria exhibited proliferative LN when biopsied. The nomogram including clinical, urinary and laboratory parameters might help with the prediction of proliferative LN before biopsy among patients with low-level proteinuria.
Post-Traumatic Hip Osteoarthritis after Pelvic Ring Injuries
Authors: Brodell James D. , Shaikh Hashim J.F. , Rodenhouse Thomas F. , Giordano Brian D. , Ketz John P. , Soin Sandeep P. , Joseph Noah M.
Published: January 2025

OBJECTIVES:

While rates of post-traumatic osteoarthritis after acetabulum fracture have been thoroughly studied, there has been less emphasis on hip osteoarthritis after pelvic ring injuries. The objective of this study was to determine the frequency of post-traumatic hip osteoarthritis in pelvic ring injury patients. It was hypothesized that more severe pelvic ring injuries would be associated with greater rates of post-traumatic hip osteoarthritis.

METHODS:

Design: Retrospective Cohort

Setting:

Urban/Suburban Academic Level I Trauma Center

Patient Selection Criteria:

Subjects were identified using a retrospective search for AO/OTA type A, B, and C pelvic ring injuries. Patients were included if they were age 18 or greater, had a pelvic ring injury, and one year or more of radiographic follow-up. Patients were excluded if they had prior total or hemi-arthroplasty of either hip, femoral neck fracture, acetabulum fracture, femoral head fracture, or inadequate radiographic follow-up.

Outcome Measures and Comparisons:

Both hips were graded using the Tönnis classification at the time of injury and available follow-up pelvis films. Comparison of rate of osteoarthritis progression was made between stable (LC I injuries stable on examination under anesthesia, all APC I injuries) and unstable (APC II, APC III, LC II, LC III, LC I injuries unstable on examination under anesthesia) pelvic ring injury patients, as well as severity of injury using the Young-Burgess classification.

RESULTS:

Two hundred and eleven patients were included for final analysis. Average age was 58.8 years (SD 28.1 years, range 18-100 years). Eighty-eight patients (41.7%) were male. 127 patients underwent non-operative management, and 84 underwent surgical stabilization. 34.5% (29/84) of patients with unstable pelvic ring injuries and 6.2% (8/127) of patients with stable pelvic ring injuries demonstrated progression of osteoarthritis on the ipsilateral side of their injury (p < 0.001). More severe pelvic ring injury patterns had a greater rate of post-traumatic osteoarthritis (PTOA) based on the Young-Burgess injury classification (44.4% of LC III versus 11.1% of LC I pelvic ring injury patients, p < 0.001).

CONCLUSIONS:

A significant frequency of post-traumatic osteoarthritis after pelvic ring injuries was identified. A higher rate of preogression to PTOA was found with unstable injuries compared with stable pelvic injuries.

LEVEL OF EVIDENCE:

III, Retrospective Cohort Study
The Use of Fresh Osteoarticular Allografts for Steroid-induced Osteonecrosis of the Femoral Condyle With Collapse in Childhood Cancer Patients: Single-institutional Experience
Authors: Neel Michael D. , Murphy Sandra W. , Kaste Sue C. , Defeo Brian M. , Karol Seth E. , Klug Patrick B. , Houston Mary B. , Weiss Kenneth S.
Published: January 2025

Background:

Despite success in treating childhood acute lymphoblastic leukemia and lymphoma (ALL), modern multiagent chemotherapy regimens containing high-dose corticosteroids can result in osteonecrosis afflicting survivors, frequently involving the knee. Thus, we describe the usage of fresh osteoarticular allograft (FOAG) to treat steroid-induced osteonecrosis of the femoral condyle in pediatric cancer survivors. We assessed the efficacy of FOAGs to heal necrotic bone, provide long-term pain relief, while retrospectively reviewing quality of life and functional status.

Methods:

We recorded patient demographics, pain, and functional scores preoperatively, postoperatively, and at the most recent follow-up, additional surgical procedures, and radiographic outcomes at each timepoint. Anatomic locations and sizes of the grafts were noted using operative reports and intraoperative photographs. Function and pain scores were collected by direct patient communication or through survey, with data scored using the KOOS (Knee Injury and Osteoarthritis Outcome Score), PROMIS (Patient-Reported Outcomes Measurement Information System), and CTCAE (Common Terminology Criteria for Adverse Events) scoring tools.

Results:

Eighteen patients, (12 females) over a period of 8 years, underwent the procedure. One patient was excluded due to death before 12 months follow-up. The average age at diagnosis of femoral condyle osteonecrosis was 14.5 years. The average age at the time of surgery was 18.5 years (range, 13 to 25 y). All patients had at least 16 months follow-up (average 60 mo; range 16 to 99 mo). Grafts ranged in size from 18 to 27.5 mm. All patients reported a return to normal function of the knees with KOOS scores approaching normal, PROMIS scores averaging 46, and CTCAE outcomes improving at an average of 34 months post-surgery. Two patients experienced a partial graft failure, which was repaired with new allografts.

Conclusions:

Although historical reviews indicated unsatisfactory results, our experience highlights the successful usage of FOAG for the management of patients treated for childhood leukemia who develop steroid-induced osteonecrosis of the femoral condyle. This procedure proved effective in managing pain and improving function and quality of life, with good bone ingrowth despite large necrotic lesions.

Levels of Evidence:

Therapeutic Level IV.
Feasibility and safety of Taipei Veterans General Hospital Heavy Ion Therapy Center: The first carbon-ion irradiation facility in Taiwan
Authors: Lan Tien-Li , Shiau Cheng-Ying , Wang Ling-Wei , Liu Yu-Ming , Chen Yi-Wei , Huang Pin-I , Hu Yu-Wen , Lai I-Chun , Wu Yuan-Hung , Lai Tzu-Yu , Kang Yu-Mei , Yang Wan-Chin , Lin Yu-Jung , Pan Yi-Ying , Chiu Chi-Chuan , Liu Ching-Sheng , Hsieh Tung-Sheng , Lee Jia-Cheng , Lin Fang-Yi , Chan Chien-Hsuan , Lin Hui-Chia , Lan Keng-Li
Published: January 2025

Background:

Unlike conventional photon radiotherapy, particle therapy has the advantage of dose distribution. Carbon-ion radiotherapy is also advantageous in terms of biological effectiveness and other radiobiological aspects. These benefits lead to a higher response probability for previously known radioresistant tumor types. Therefore, Taipei Veterans General Hospital, which is located in the northern district of Taipei, built the first carbon-ion irradiation facility in Taiwan.

Methods:

Taipei Veterans General Hospital completed a phase 1 trial to evaluate the safety of carbon-ion radiotherapy. Six patients (4 males and 2 females with prostate adenocarcinoma, sacral chordoma, hepatocellular carcinoma, lung adenocarcinoma, or parotid high-grade carcinoma) were enrolled in this study. The mean age of the patients was 62.7 years. The mean dose was 57.3 Gy(RBE) (fraction range, 4-16 Gy(RBE)).

Results:

During this phase 1 trial, all patients were monitored for 3 months to evaluate acute toxicity and short-term outcomes after treatment with carbon irradiation. Only 2 patients experienced grade 2 toxicity, which resolved without medication 1 month after completing treatment. The tumor response demonstrated 1 complete response, 1 partial response, and 4 cases of stable disease.

Conclusion:

Carbon-ion radiotherapy was determined to be an effective and safe treatment.
Potential risk factors for delayed neurological sequelae and myocardial injury following acute carbon monoxide poisoning: A retrospective study
Authors: Ho Min-Po , Wu Yuan-Hui , Chen Tsan-Chi , Tsai Kuang-Chau , Yang Chen-Chang
Published: January 2025

Background:

Acute carbon monoxide poisoning (COP) has been a common cause of emergency hospital visits over the past decade. Besides the immediate symptoms of poisoning, carbon monoxide exposure can cause various long-term complications, especially delayed neurological sequelae (DNS) and myocardial injury (MI).

Methods:

This study retrospectively enrolled 502 patients with COP, including complete collection data, from the Taiwan National Poison Control Center between January 1, 2000, and December 31, 2015. After collecting the relevant clinical and laboratory data, multivariate logistic regression analysis was performed to investigate the associations between potential predictors and risk factors, hazard ratio (HR), and confidence intervals (CI).

Results:

The cumulative incidence rates were 12.0% and 19.7% for DNS and MI, respectively. A Glasgow Coma Scale (GCS) score of <9 (HR 2.55; 95% CI: 1.52–4.27) and rhabdomyolysis (HR 2.68; 95% CI: 1.59–4.53) were identified as individual indicators of DNS in patients with COP. However, a greater risk for MI was associated with a GCS score of <9 (HR 2.50; 95% CI: 1.67–3.74), rhabdomyolysis (HR 4.91; 95% CI: 3.28–7.35), acute renal impairment (HR 2.43; 95% CI: 1.59–3.71), and leukocytosis (HR 9.55; 95% CI: 3.88–23.50). Hyperbaric oxygen therapy for patients with COP was more beneficial for DNS (HR 0.64; 95% CI: 0.34–1.20) than for MI (HR 1.94; 95% CI: 0.94–4.01).

Conclusion:

Early differentiation of risk factors between DNS and MI contributes to an effective evaluation of patients with acute COP and the provision of appropriate therapy.
Comparison of long-term outcomes of minimally invasive coronary artery bypass grafting and percutaneous coronary intervention for left main disease
Authors: Güner Ahmet , Can Cemil , Bedir Fatih Furkan , Aydin Ünal , Kadiroğullari Ersin , Akman Cemalettin , Gültekin Güner Ezgi , Aydin Emre , Serter Berkay , Çizgici Ahmet Yaşar , Aktürk İbrahim Faruk , İyigün Taner , Aksu Timuçin , Doğan Abdullah , Aydin Merve , Şimşek Aybüke , Uzun Fatih
Published: January 2025

Background

Minimally invasive coronary artery bypass grafting (MICS-CABG) is frequently used for coronary revascularization, but the comparison of long-term clinical results with percutaneous coronary intervention (PCI) in left main disease (LMDs) remains unclear. The present study sought to determine the long-term outcomes of MICS-CABG and PCI in patients with LMDs.

Methods

A total of 551 consecutive patients [man: 457 (82.9%), mean age: 60.70 ± 9.54 years] who underwent PCI or MICS-CABG for LMDs were included. The primary endpoint was defined as the all-cause death during follow-up. The secondary endpoint defined as the major cardiovascular and cerebral events (MACCE) included cardiac death, myocardial infarction, target vessel revascularization, stroke, and stent thrombosis or graft occlusion. Inverse probability weighting (IPW) was performed to reduce treatment selection bias. This is the first report comparing the long-term outcomes of MICS-CABG and PCI in patients with LMDs.

Results

The initial revascularization strategy was MICS-CABG in 269 (48.8%) cases and PCI in 282 (51.2%) patients. The SYNTAX scores (31.25 ± 4.63 vs. 26.05 ± 5.9, P < 0.001) were notably higher in the MICS-CABG group than in the PCI group. The incidence of long-term mortality (11 vs. 5.6%, P = 0.022) and MACCE (22 vs. 15.2%, P = 0.042) were notably higher in the PCI group than in the MICS-CABG group. The long-term mortality [adjusted HR (IPW) = 6.38 (95% CI, 3.00–13.57), P < 0.001] and MACCE [adjusted HR (IPW) = 4.51 (95% CI, 2.90–7.03), P < 0.001] in the overall population significantly differed between the PCI group and the MICS-CABG group.

Conclusion

The present study suggests that MICS-CABG for LMDs was associated with lower long-term mortality and MACCE rates than PCI.
Cholangioblastic Cholangiocarcinoma (NIPBL::NACC1 cholangiocarcinoma)
Authors: Argani Pedram , Oshima Kiyoko , Anders Robert A. , Gonzalez Raul S. , Yilmaz Osman , Bal Munita , Rooper Lisa , Hicks Jessica , De Marzo Angelo , Gagan Jeffrey , Zhu Chengsong , Palsgrove Doreen N.
Published: January 2025

The cholangioblastic variant of intrahepatic cholangiocarcinoma is a distinctive neoplasm that typically affects young women without underlying liver disease. Morphologically, it demonstrates solid, trabecular, and tubulocystic architecture, biphasic small cell-large cell cytology, and immunoreactivity for inhibin, neuroendocrine markers, and biliary but not hepatocellular markers. In 2021, our group identified a characteristic NIPBL::NACC1 gene fusion in cholangioblastic cholangiocarcinoma, and since then ~20 genetically confirmed cases have been reported in the literature. We report 2 additional cases, both of which caused diagnostic challenges. The first was previously published as a “biliary adenofibroma with malignant features” which we now show recurred as a high-grade adenocarcinoma. Re-review of the original lesion demonstrated the morphologic and immunohistochemical features of highly cystic cholangioblastic cholangiocarcinoma, whereas the high-grade recurrence lacked many of these features. In addition to the characteristic NIPBL::NACC1 gene fusion, the recurrence demonstrated loss of the RB1 and PTEN genes which were found in the highly cystic, bland areas of the original tumor, suggesting that the recurrence was derived from this bland component. The second case was originally misclassified as metastatic well-differentiated neuroendocrine neoplasm and only focally demonstrated the characteristic biphasic small cell-large cell cytology. In addition, a review of 7 cholangioblastic cholangiocarcinomas in our files demonstrates that loss of chromosome 13q14.2 (where the RB1 gene resides) and loss of chromosome 6q15-q16.3 are recurrent secondary changes in these neoplasms. Expression profiling demonstrated alterations in the transforming growth factor receptor beta superfamily, and overexpression of MYC which was validated by immunohistochemistry. Our findings expand the morphologic and genetic spectrum of this neoplasm and provide insight into secondary genetic changes associated with progression.
Antioxidant, digestive enzyme activity, and anti-inflammatory effect of plant mixture including Scutellaria baicalensis
Authors: Lee SooJung , Chung Mi Ja
Published: January 2025

The objective of this study was to identify functional materials with potential benefits for digestive enzyme activity, anti-inflammatory effects, and antioxidant activity. The study evaluated water extracts from Pyrus pyrifolia Nakai (PP), malt (MA), Ziziphus jujuba Mill. (ZJ), Leonurus japonicus Houtt. (LJ), Scutellaria baicalensis (SB), and various mixtures of these. These extracts were concentrated, lyophilized, and labeled as PPW, MAW, ZJW, LJW, SBW, Mix1, Mix2, Mix3, Mix4, and Mix5. Among all the samples tested, Mix3, composed of PP, MA, ZJ, LJ, and SB in a ratio of 1:1:2:1:2 (w/w), showed the most promising results. It exhibited the highest DPPH radical scavenging activity at a concentration of 1,000 μg/mL. Mix3 showed the highest total polyphenol content compared to the other mixtures. The study also assessed the anti-inflammatory effects of the extracts by measuring the levels of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide (LPS)-stimulated Caco-2 cells. Mix3 was found to suppress the production of both NO and TNF-α significantly. Additionally, the digestive enzyme activity of the samples was evaluated. Mix3 demonstrated superior lipase and α-amylase activities at 100 μg/mL, as well as comparable or higher trypsin activity at 500 μg/mL when compared to other extracts. These findings suggest that Mix3 enhances digestive enzyme activities and anti-inflammatory effect, making it a potential functional material for improving digestion.
Inulin fructans: Fermentability in the human colon, health benefits
and quantification
Authors: Mudannayake Deshani C. , Jayasena Dinesh D. , Ranadheera C. Senaka , Ajlouni Said
Published: January 2025

Inulin fructans are non-digestible polysaccharides of the fructan family that are
composed of monomers of fructose joined by β-(2-1) glycosidic
(fructosyl-fructose) linkages with varying degrees of polymerization. Inulin
fructan has numerous functional and health benefits, which have fueled market
demand remarkably as a functional food ingredient during the last several years.
Recent human and animal clinical trials have revealed that inulin can enhance
the saccharolytic fermentation over proteolytic fermentation in the colon,
thereby increasing short-chain fatty acid and lactic acid production, which in
turn deliver numerous health benefits, including gut microflora modulation,
enhancing mineral absorption and reducing the risk of colon cancers. With the
rising popularity and use of inulin, there has been increasing research interest
in determining the quality and quantity of inulin fructans. Quantification of
inulin has become challenging since plants contain inulin with a varying degree
of polymerization in a range of 3-60. Various techniques have been used to
quantify fructans, including diverse chromatographic and enzyme-involved
spectrometric techniques. Despite there are many reviews on inulin as a
functional food, few compiles accepted quantification methods of inulin. This
review offers a concise guide on the theoretical principles behind the accepted
analytical methods of quantification of inulin, in addition to the
fermentability of inulin in the human colon and its potential health
benefits.
Modification of inulin for improved encapsulation efficiency and controlled release of quercetin
Authors: Aliya Khanafina , Cho Ha-Seong , Olawuyi Ibukunoluwa Fola , Lee Won-Young
Published: January 2025

Quercetin (Q) was encapsulated with inulin (In) and acetylated inulin (AcIn) through a freeze-drying process to increase its stability and bioavailability. Hence, the difference in structure, encapsulation, and morphology properties, as well as release study between encapsulated quercetin with inulin (In-Q) and acetylated inulin (AcIn-Q) were investigated. The successful modification of inulin into acetylated inulin and the encapsulation of quercetin within the In and AcIn matrixes were confirmed by the Fourier Transform Infrared (FT-IR) analysis. In terms of encapsulation efficiency and loading capacity, AcIn-Q showed higher (82.74% and 32.85%) than In-Q (80.69% and 22.22%), respectively (p<0.05). In addition, scanning electron microscopy (SEM) analysis showed that the AcIn-Q encapsulated showed more uniform, spherical particles with smoother surfaces than In-Q. Moreover, AcIn-Q exhibited a more significant stable quercetin release pattern than the In-Q in vitro test. From the release kinetic assay, the release profile of AcIn-Q and In-Q were fitted to the Korsmeyer-Peppas model based on the correlation coefficient (R2>0.95). Additionally, AcIn-Q was controlled by a non-Fickian diffusion mechanism, while In-Q was regulated by Fickian diffusion. In summary, our study proposes the encapsulation of quercetin with acetylated inulin as an encapsulation agent through freeze-drying to improve release kinetics and the potential application for therapeutic efficacy.
Development of brandy production technology using high-alcohol wine and quality characteristics of brandy aged with oak chips through accelerated aging
Authors: Lee Jueun , Kang Jieun , Kim Chanwoo , Lim Bora , Hwang Inseo , Han Guijeong , Kim Youngmi , Choi Jiho
Published: January 2025

This study evaluated the effects of single distillation using a 30 °Brix high-alcohol wine and accelerated aging with oak chips on the quality characteristics of brandy. By distilling 30 °Brix fermented wine, we obtained a distillate with an alcohol concentration of approximately 43.27%, confirming the feasibility of producing high-proof brandy without secondary distillation. Additionally, during oak chip aging, lightness (L*) decreased by about 30%, while redness (a*) and yellowness (b*) values increased by approximately 20% and 70%, respectively, enhancing the brandy’s depth of color. According to electronic tongue analysis, oak chip aging contributed to an increase in umami, resulting in a more balanced flavor profile. Preference tests indicated that accelerated aging with medium and dark oak chips for 2 and 4 weeks enhanced vanilla, oak, and roasted flavors, increasing overall preference. PCA analysis showed that the sample aged with medium oak chips after a single distillation of the 30 °Brix wine was in the same quadrant as commercial imported brandy along the DF1 axis, suggesting the industrial applicability of using high-alcohol fermented wine and oak chip-based accelerated aging for brandy production.
Single-Walled Carbon Nanotube Probes for Protease Characterization Directly in Cell-Free Expression Reactions
Authors: Hejazi Sepehr , Godin Ryan , Jurasic Vito , Reuel Nigel F
Published: January 2025

Proteins can be rapidly prototyped with cell-free expression (CFE) but in most cases there is a lack of probes or assays to measure their function directly in the cell lysate, thereby limiting the throughput of these screens. Increased throughput is needed to build standardized, sequence to function data sets to feed machine learning guided protein optimization. Herein, we describe the use of fluorescent single-walled carbon nanotubes (SWCNT) as effective probes for measuring protease activity directly in cell-free lysate. Substrate proteins were conjugated to carboxymethyl cellulose-wrapped SWCNT, yielding stable and sensitive probes for protease detection with a detection limit of 6.4 ng/mL for bacterial protease fromStreptomyces griseus. These probes successfully measured subtilisin activity in unpurified CFE reactions, surpassing commercial assays. Furthermore, they enabled continuous monitoring of activity during synthesis of subtilisin in both purified and lysate-based CFE systems without compromising protein expression. Surface passivation techniques, such as pre-incubation with cell lysate and supplement components, reduced the initial signal loss and improved probe signal stability in the complex cell lysate environment. These modular probes can be used, as described, for high-throughput screening and optimization of proteases and, with the change of conjugated substrate, a wider range of other hydrolases.
Roles of Cro2and CI2binding to ORoperators in controlling lysogeny stability during prophage induction
Authors: Pang Yiyu , Lei Xue , Manuchehrfar Farid , Du Lin , Liang Jie
Published: January 2025

The lysogeny-lysis switch in bacteriophage lambda serves as a model for understanding cell fate decisions. The molecular network controlling this switch has been explored through extensive experimental and computational studies. Yet, the specific role of protein-DNA interactions, like the binding of CI2and Cro2proteins to operator sites, in regulating lysogeny stability during prophage induction remains less under-stood. This study employs a minimalistic model and the Accurate Chemical Master Equation (ACME) method to construct detailed probability landscapes of the network’s behavior under varying conditions, such as different dissociation and CI2degradation rates which simulate UV irradiation effects. Our findings indicate that Cro2binding at OR3 and CI2at OR1 significantly influence lysogeny stability, with the former destabilizing and the latter stabilizing it. Conversely, interactions at OR1 by Cro2and OR3 by CI show minimal impact on this stability. Through the ACME approach, we could examine the network’s global behavior under conditions unapproachable by conventional stochastic simulations. This study highlights the critical roles of specific protein-DNA interactions in maintaining lysogeny and provides insight into the broader dynamics of the lysogeny-lysis switch under various physiological stresses.
Effect of improved spatial resolution on PET SUVR estimates in the LEADS study of sporadic early-onset Alzheimer’s disease
Authors: Schonhaut Daniel R. , La Joie Renaud
Published: January 2025

Background

The Longitudinal Early-onset Alzheimer’s Disease Study (LEADS) recently transitioned from processing positron emission tomography (PET) scans at 8mm to 6mm resolution in early 2024. Concurrent with this improved spatial resolution, we revised our processing methods for defining reference regions used in amyloid and tau PET analyses, with the goal to maintain alignment with MRI-based PET processing in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Methods

We describe the following changes to the LEADS MRI-based PET processing pipeline:

Transition from 8mm to 6mm PET scans.

Revised method to calculate a composite reference region scaling factor for longitudinal analysis of18F-Florbetaben (FBB).

Revised method to define the eroded subcortical white matter region, which is used in longitudinal analyses of both FBB and18F-Flortaucipir (FTP).

Corrected method to define the inferior cerebellar gray matter reference region used in cross-sectional analysis of FTP.

We evaluated these changes by comparing 8mm standardized uptake value ratios (SUVRs) processed with the original LEADS PET pipeline to 6mm SUVRs processed with the updated pipeline. This analysis was conducted in 564 FBB, 555 FTP, and 134 FDG scans acquired in LEADS participants at baseline between May 2018 and September 2023.

Results

We found near-perfect correlations across all tracers and reference regions (R2> 0.99). However, 6mm SUVRs had greater dynamic range than 8mm SUVRs, with 8mm-to-6mm linear transformation slopes ranging from 1.08 to 1.22.

Conclusions

Our findings closely parallel ADNI’s experience transitioning to higher resolution PET. Amyloid PET Centiloid conversion equations, which were originally derived using 8mm data, should be re-estimated using 6mm data to maintain optimal harmonization. LEADS data users should not mix 6mm and 8mm PET data and should instead exclusively use 6mm PET data going forward, as these measures better reflect modern scanner capabilities while maintaining compatibility with ADNI. LEADS data users who are unsure of the origin or resolution of their PET values are encouraged to contact us for advice atLEADS.PETCORE@ucsf.edu.
Toward highly accurate reference and method selection for universal cross-dataset cell type annotation
Authors: Shen Qunlun , Zhang Shuqin , Zhang Shihua
Published: January 2025

Cell type annotation is a critical and essential task in single-cell data analysis. Various reference-based methods have provided rapid annotation for diverse single-cell data. However, how to select the optimal references and methods is often overlooked. To this end, we present a cross-dataset cell-type annotation methodology with a universal reference data and method selection strategy (CAMUS) to achieve highly accurate and efficient annotations. We demonstrate the advantages of CAMUS by conducting comprehensive analyses on 672 pairs of cross-species scRNA-seq datasets. The annotation results with references selected by CAMUS achieved substantial accuracy gains (25.0-124.7%) across five reference-based methods. CAMUS achieved high accuracy in choosing the best reference-method pair among 3360 pairs (49.1%). Combined with reference-integrated strategies, they improved further on 3522 dataset triplets (9.3-39.3%). Moreover, CAMUS showed high accuracy in selecting the best methods on the 80 scST datasets (82.5%) and five scATAC-seq datasets (100.0%), illustrating its universal applicability. In addition, we utilized the CAMUS score with other metrics to predict the annotation accuracy, providing direct guidance on whether to accept current annotation results.
Direct binding of arsenicals to nuclear transport factors disrupts nucleocytoplasmic transport
Authors: Lorentzon Emma , Lee Jongmin , Masaryk Jakub , Keuenhof Katharina , Karlsson Nora , Galipaud Charlotte , Madsen Rebecca , Höög Johanna L. , Levin David E. , Tamás Markus J.
Published: January 2025

Human exposure to arsenicals is associated with devastating diseases such as cancer and neurodegeneration. At the same time, arsenic-based drugs are used as therapeutic agents. The ability of arsenic to directly bind to proteins is correlated with its toxic and therapeutic effects highlighting the importance of elucidating arsenic-protein interactions. In this study, we took a proteomic approach and identified 174 proteins that bind to arsenic inSaccharomyces cerevisiae. Proteins involved in nucleocytoplasmic transport were markedly enriched among the arsenic-binding proteins, and we demonstrate that arsenic-binding to nuclear import factors results in their relocation from the nuclear envelope and subsequent aggregation in the cytosol. Similarly, nuclear pore proteins that make up the nuclear pore complex mislocalized and aggregated in arsenic-exposed cells. Consequently, arsenic was shown to inhibit nuclear protein import and export. We propose a model in which arsenic-binding to nuclear transport factors leads to their mislocalization and aggregation, which disrupts nucleocytoplasmic transport and causes arsenic sensitivity.
Behavior decoding delineates seizure microfeatures and associated sudden death risks in mice
Authors: Shen Yuyan , Thomas Jaden , Chen Xianhui , Zelidon Jaden , Hahn Abigayle , Zhang Ping , Sathyanesan Aaron , Gu Bin
Published: January 2025

Behavior and motor manifestations are distinctive yet often overlooked features of epileptic seizures. Seizures can result in transient disruptions in motor control, often organized into specific behavioral patterns that can inform seizure types, onset zones, and outcomes. However, refined analysis of behaviors in epilepsy remains challenging in both clinical and preclinical settings. Current manual video inspection approaches are subjective, time-consuming, and often focus on gross and ambiguous descriptions of seizure behaviors, overlooking much of the intricate behavioral dynamics and action kinematics. Here, we utilized two machine learning-aided tools,DeepLabCut(DLC) andBehavior Segmentation of Open Field in DLC(B-SOiD), to decode previously underexplored behavior and action domains of epilepsy. We identified 63 interpretable behavior groups during seizures in a population of 32 genetically diverse mouse strains. Analysis of these behavior groups demonstrates significant differential behavior expression and complexity that can delineate distinct seizure states, unravel intrinsic seizure progression over time, and inform mouse strain backgrounds and genotypes. We also identified seizure behavior patterns and action/subaction kinematics that determine the risks of sudden unexpected death in epilepsy (SUDEP). These findings underscore the significant potential for translation into inpatient settings for video analysis in epilepsy monitoring units and outpatient settings via home surveillance devices and smartphones.

One Sentence Summary

AI-aided behavior decoding delineates intricate seizure microfeatures in mice.
Microbiome and Genetic Predictors of Weight Loss 12 Months Post Sleeve Gastrectomy: Insights from a Pilot Retrospective Cohort Study
Authors: Pedroso Inti , Kumbhare Shreyas V. , Johnson Shaneeta , Muthukumar Karthik M. , Saravanan Santosh K. , Irudayanathan Carmel , Sharma Garima , Tabone Lawrence , Sinha Ranjan , Almonacid Daniel E. , Szoka Nova
Published: January 2025

Background

Gut microbiome and genetic biomarkers are increasingly guiding obesity treatment. Bariatric surgery leads to shifts in gut microbial composition and function, while genome-wide association studies reveal genetic underpinnings of polygenic obesity, informing risk, therapeutic outcomes, and nutrigenomics-based interventions.

Objectives

This pilot study aimed to identify gut microbiome and genetic biomarkers associated with weight loss 12 months after sleeve gastrectomy (SG).

Setting

Single academic institution university clinic

Methods

Sixty-seven patients 12 months post-SG were enrolled: 34 had successful excess weight loss (EWL≥50%), while 33 had unsuccessful EWL (EWL<50%). Microbiome and genetic profiles were collected and analyzed using ANOVA and regression methods.

Results

The genus Akkermansia was significantly associated with EWL (p=9.9×10^−6). Several microbial pathways, including propionate synthesis and menaquinone (vitamin K2) production, showed nominally significant (p<0.05) associations with greater weight loss. No differences emerged in the Firmicutes/Bacteroidetes ratio. Genetic analyses revealed significant correlations between EWL and polygenic scores for dietary needs and metabolic responses, including distinct vitamin D and K requirements, as well as higher LDL cholesterol levels and predisposition for major depression.

Conclusion

These findings suggest that both the gut microbiome and genetics may modulate weight loss following bariatric surgery. Integrating microbiome and genetic profiling into bariatric care pathways could enhance personalized obesity treatment. While this pilot, exploratory, and proof-of-concept study has limitations, it supports prior work linking gut microbial pathways to weight loss and suggests new associations. Follow-up studies are warranted to validate these results and further inform precision obesity interventions.

Highlights

Akkermansia strongly correlates with weight loss 12 months post-sleeve gastrectomy.

Microbiome propionate and vitamin K2 pathways linked to higher excess weight loss.

Genetic markers link vitamin needs, LDL and depression risk with lower weight loss.

Microbiome and genetics integration may improve bariatric surgery outcomes.
Noncanonical EEG-BOLD coupling by default and in schizophrenia
Authors: Jacob Michael S. , Roach Brian J. , Mathalon Daniel H. , Ford Judith M.
Published: January 2025

Neuroimaging methods rely on models of neurovascular coupling that assume hemodynamic responses evolve seconds after changes in neural activity. However, emerging evidence reveals noncanonical BOLD (blood oxygen level dependent) responses that are delayed under stress and aberrant in neuropsychiatric conditions. To investigate BOLD coupling to resting-state fluctuations in neural activity, we simultaneously recorded EEG and fMRI in people with schizophrenia and psychiatrically unaffected participants. We focus on alpha band power to examine voxelwise, time-lagged BOLD correlations. Principally, we find diversity in the temporal profile of alpha-BOLD coupling within regions of the default mode network (DMN). This includes early coupling (0-2 seconds BOLD lag) for more posterior regions, thalamus and brainstem. Anterior regions of the DMN show coupling at canonical lags (4-6 seconds), with greater lag scores associated with self-reported measures of stress and greater lag scores in participants with schizophrenia. Overall, noncanonical alpha-BOLD coupling is widespread across the DMN and other non-cortical regions, and is delayed in people with schizophrenia. These findings are consistent with a “hemo-neural” hypothesis, that blood flow and/or metabolism can regulate ongoing neural activity, and further, that the hemo-neural lag may be associated with subjective arousal or stress. Our work highlights the need for more studies of neurovascular coupling in psychiatric conditions.
Clinical and Taxonomic Characterization of a Novel Urinary Tract PathogenProvidencia lanzhouensis
Authors: Xiang Yanghui , Dong Xu , Ma Lan , Cao Dan , Li Yi , Jiang Xiuzhi , Xu Pusheng , Yuan Xin , Bi Kefan , Zhang Yiru , Han Yuxin , Zhang Ying
Published: January 2025

Background

The genusProvidenciaincludes species of ecological and clinical significance, with some acting as opportunistic pathogens in hospital-acquired infections such as urinary tract infection (UTI). However, overlapping phenotypic traits and genetic similarities pose challenges for accurate species characterization. This study exemplifies this challenge by identifying a novelProvidenciaisolate through genomic analysis.

Results

In this study, strain PAZ2 was isolated from the urine sample of a hospitalized patient in Lanzhou, Gansu Province, China. Initial mass spectrometry analysis identified the strain asProvidencia alcalifaciens. It exhibits a resistance profile against antibiotics including ampicillin, tetracycline, tigecycline, polymyxin B, colistin, trimethoprim-sulfamethoxazole, and ciprofloxacin. However, whole-genome sequence analysis indicated that this strain is a novel species with an average nucleotide identity (ANI) values ranging from 79.92% to 94.73% and digital DNA-DNA hybridization (dDDH) values between 21.2% and 57.6% when compared with all knownProvidenciaspecies. Furthermore, strain PAZ2 exhibited unique biochemical properties that differentiated it from all previously described species within the genus.

Conclusions

Genomic and biochemical evidence supports PAZ2 as a novelProvidenciaspecies, which we namedProvidencia lanzhouensissp. nov. This finding enhances the taxonomy ofProvidenciaand underscores its clinical relevance, notably in UTIs and other nosocomial infections. Accurate identification is crucial for guiding effective treatment and preventing misdiagnosis. Further studies should investigate its pathogenicity, antimicrobial resistance, and epidemiology to inform infection control measures.
N-acetylcysteine to reduce kidney and liver injury associated with drug-resistant tuberculosis treatment
Authors: Meadows Idu , Mvungi Happiness , Salim Kassim , Kaswaga Oscar , Mbelele Peter , Liyoyo Alphonce , Semvua Hadija , Ngoma Athumani , Heysell Scott , Mpagama Stellah
Published: January 2025

Background

New drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated.

Method

A randomized controlled trial (PACTR202007736854169) was conducted at Kibong’oto Infectious Disease Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan-Meier curves were employed to compare group event occurrences.

Results

66 patients (mean age 47±12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice daily group (p>0.99). Severe AEs were observed in 4 patients in the standard group, 2 in the NAC 900 mg daily group, and 3 in the NAC 900 mg twice daily group. Renal toxicity was more prevalent in the standard treatment group (45% vs. 23%; p=0.058), with a shorter onset of time to toxicity (χ2 = 3.199; p=0.074). Liver injury events were rare across all groups.

Conclusion

Among Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.