bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial cargo export in exosomes: Possible pathways and implication in disease biology
Authors: Sharma Aman 
Published: February 2023

AbstractExosome biogenesis occurs parallel to multiple endocytic traffic routes. These coexisting routes drive cargo loading in exosomes via overlapping of exosome biogenesis with endosomal pathways. One such pathway is autophagy which captures damaged intracellular organelles or their components in an autophagosome vesicle and route them for lysosomal degradation. However, in case of a noncanonical fusion event between autophagosome and maturing multivesicular body (MVB)—a site for exosome biogenesis, the autophagic cargo is putatively loaded in exosomes and subsequent released out of the cell via formation of an “amphisome” like structure. Similarly, during “mitophagy” or mitochondrial (mt) autophagy, amphisome formation routes mitophagy cargo to exosomes. These mt‐cargo enriched exosomes or mt‐enREXO are often positive for LC3 protein—an autophagic flux marker, and potent regulators of paracrine signaling with both homeostatic and pathological roles. Here, I review this emerging concept and discuss how intracellular autophagic routes helps in generation of mt‐enREXO and utility of these vesicles in paracrine cellular signaling and diagnostic areas.
Pancreatic adverse events in patients treated with immune checkpoint inhibitors
Authors: Hana Caroline , Rehman Tauseef , Park Kyeeun , Carracedo Uribe Carlos , Aung Pyi Phyo , Hunis Brian , Salzberg Matthew , Zikria Jennifer , Hussein Atif 
Published: February 2023

AbstractBackground and AimThe inhibition of cytotoxic T‐lymphocyte associated antigen‐4 (CTLA‐4) and programmed cell death‐1 (PD‐1) has been a target for multiple drugs to enhance the T‐cell antitumor activity. However, these immune checkpoint inhibitors (ICIs) come with a panel of immune‐related adverse events (irAEs) that include mainly endocrine, skin, and gastrointestinal effects. We report seven cases of pancreatic irAEs in patients treated with ICIs at our institute.MethodsThis is a case series; data was collected through chart review by 3 different data collectors and was analyzed separately by 2 physicians.ResultsOf these seven cases, two had diabetic ketoacidosis (DKA), while five had pancreatitis diagnosed by a substantial rise in serum lipase. Pancreatitis was asymptomatic in two cases. A pancreatic biopsy in one case revealed type 2 autoimmune pancreatitis. The ICIs used included pembrolizumab, nivolumab, durvalumab, and avelumab. Treatment included steroids and holding the ICI therapy: three cases had complete resolution of pancreatitis while two cases required either a prolonged taper or a second course of prednisone for recurrence of pancreatitis. On the other hand, the DKA cases were treated with withdrawal of the ICI and starting insulin with no steroid therapy.ConclusionsPancreatitis and DKA are rare adverse events of ICIs that can be controlled by holding the ICI with or without starting steroids. Rechallenging the patient with the same ICI is possible in selected cases.
MYC‐activated LINC00607 promotes hepatocellular carcinoma progression by regulating the miR‐584‐3p/ROCK1 axis
Authors: Dong Shuilin , Wang Wei , Liao Zhibin , Fan Yawei , Wang Qi , Zhang Lei 
Published: February 2023

AbstractBackgroundThere have been many reports of long non‐coding RNAs (lncRNAs) in tumors, and abnormally expressed lncRNA is closely related to hepatocellular carcinoma (HCC). The mechanism of LINC00607 in HCC has not been reported.MethodsWe utilized qPCR to evaluate the RNA expression level. The mechanism of MYC binding to the LINC00607 promoter was revealed through chromatin immunoprecipitation assay and dual luciferase reporter assay. The proliferation and invasive ability were evaluated by CCK‐8 and transwell assays. The relation between LINC00607 and miR‐584‐3p was assessed by RNA immunoprecipitation assay and dual luciferase reporter assay. The level of ROCK1 was evaluated by qPCR and western blot.ResultsIn this research, we found that the expression of LINC00607 was higher in HCC tissues when compared with that in the adjacent non‐tumor tissues. Meanwhile, MYC was observed to interact with the LINC00607 promoter, leading to the upregulation of LINC00607 in HCC. We further revealed that LINC00607 functioned as a sponge for miR‐584‐3p. Cell proliferation and migration assays showed that miR‐584‐3p may inhibit the HCC progression. Moreover, we found that the miR‐584‐3p inhibitor could reverse the effects of LINC00607 downregulation in HCC through rescue experiments. Through verification, miR‐584‐3p bound to the 3′ UTR of ROCK1 to downregulate its expression.ConclusionLINC00607 regulated by MYC can promote the proliferation, migration and invasion of HCC cells through the miR‐584‐3p/ROCK1 axis.
circANKRD28 inhibits cisplatin resistance in non‐small‐cell lung cancer through the miR‐221‐3p/SOCS3 axis
Authors: Song Shu , Shi Yuhan , Zeng Dong , Xu Jingjing , Yang Yuexiang , Guo Wenjuan , Zheng Ye , Tang Haicheng 
Published: February 2023

AbstractBackgroundNon‐small‐cell lung cancer (NSCLC) is a common cancer. Chemotherapeutic drug resistance limits the therapeutic effect of NSCLC and leads to a poor prognosis. As a result, new specific targets may be better identified by studying the mechanism of drug resistance to cisplatin in NSCLC.MethodsIn the present study, we performed a quantitative real‐time polymerase chain reaction and western blotting to detect mRNA and protein levels. The proliferation of cells was analyzed by a Cell Counting Kit‐8 and colony formation assays. Cell invasion was measured via the Transwell assay. A scratch assay was performed to measure cell migration in cisplatin (DDP)‐resistant NSCLC cells. Apoptosis of cells was examined using flow cytometry.ResultsWe found that circANKRD28 was notably decreased in NSCLC. The results showed that circANKRD28 expression was not affected, and its half‐life was more than 12 h. Functional experiments revealed that circANKRD28 overexpression inhibited DDP resistance in NSCLC cells in vitro. Mechanistic findings demonstrated that circANKRD28 regulated tumor cell progression and DDP sensitivity through the miR‐221‐3p/SOCS3 axis.ConclusionsThe present study revealed the regulatory effects and molecular mechanism of circANKRD28 on the development and cisplatin resistance in NSCLC, which may provide experimental basis and theoretical support to identify new targets for therapy of DDP resistance in NSCLC.
Posthepatectomy but not prehepatectomy chemotherapy was associated with a longer time to recurrence in patients with resectable colorectal liver metastases: Inverse probability of treatment weighting analysis
Authors: Yoshizaki Yuhi , Kawaguchi Yoshikuni , Seki Yusuke , Sasaki Shu , Ichida Akihiko , Akamatsu Nobuhisa , Kaneko Junichi , Arita Junichi , Hasegawa Kiyoshi 
Published: February 2023

AbstractBackgroundPatients with resectable colorectal liver metastases (CLM) are treated with surgery alone, surgery and posthepatectomy chemotherapy, or prehepatectomy chemotherapy and surgery. The optimal approach in terms of survival is unclear. We compared survival in the three treatment groups using inverse probability of treatment weighting (IPTW) analysis.MethodsData from patients undergoing initial CLM resection in 2005–2018 were obtained from a prospectively maintained database. Our group treated resectable CLM with surgery alone but gradually adopted post‐ and prehepatectomy chemotherapy for patients with CLM number ≥5 after 2015. IPTW analysis was employed to adjust the characteristics of the three groups.ResultsOf the 439 patients meeting the inclusion criteria, 175 underwent surgery alone, 135 underwent surgery and posthepatectomy chemotherapy, and 129 underwent prehepatectomy chemotherapy and surgery. After the IPTW adjustment, the demographic and clinicopathological characteristics were well balanced. The IPTW analysis revealed that the recurrence‐free survival was better in patients undergoing surgery and posthepatectomy chemotherapy than in patients undergoing surgery alone (median recurrence‐free survival, 1.3 years vs 0.7 years; P = .018). Overall survival was not significantly different between the three treatment approaches.ConclusionPosthepatectomy but not prehepatectomy chemotherapy prolongs the time to recurrence after curative‐intent resection of CLM.
Interdecadal Pacific Oscillation modulation of ENSO teleconnections in its decaying stages: Relations with Indian Ocean basin‐wide mode and South American precipitation
Authors: Souza Itamara P. , Andreoli Rita V. , Kayano Mary T. , Cerón Wilmar L. , Souza Rodrigo A. F. , Roy Indrani 
Published: February 2023

AbstractThis study examines the Interdecadal Pacific Oscillation (IPO) modulation of the El Niño–Southern Oscillation (ENSO) teleconnections in its decaying stages with the tropical ocean by focusing on the Indian Ocean Basin‐Wide (IOBW) mode and the precipitation over South America (SA) in the 1901–2012 period. Composite analyses revealed that the ENSO teleconnections are IPO‐modulated due to the differential ENSO decaying speed, which is slower during the positive than negative IPO phase, for both El Niño (EN) and La Niña (LN) cases. Negative precipitation anomalies related to EN persist over northeastern SA until austral winter for the positive IPO phase (POS IPO), while significant opposite sign anomalies occur in this region for the negative IPO phase (NEG IPO). These results are associated with the Walker circulation's reversal during NEG IPO which is, in turn, accompanied by negative IOBW. During the POS IPO, the positive IOBW causes upward movements over there and, by continuity, downward movements over SA. In the NEG IPO, for LN events the wave train originating in the north of Australia propagates toward subtropical SA, which, coupled with the surface circulation, causes dryness in this region. In addition, the rapid decay of LN in the NEG IPO, followed by the emergence of EN, caused changes in the Walker circulation, such that enhanced upward movements occurred over the Pacific and SA region, and downward movements over the Indian Ocean until austral winter. In turn, the slower decay of the LN in the POS IPO maintains strong subsidence over the central Pacific and weak upward motions over western SA. So, the EN (LN) and positive (negative) IOBW during the POS (NEG) IPO prolong the scarcity of precipitation over equatorial (subtropical) SA. Persistent dry periods over these regions during the ENSO decaying stage might have important implications for the seasonal forecasts.
Improvement of Robusta coffee aroma with l‐leucine powder
Authors: Jo Ara , Park Hyunbeen , Lee Seongho , Lee Kwang‐Geun 
Published: February 2023

AbstractBACKGROUNDl‐Leucine powder (LP) was added to green Robusta coffee beans in order to reduce the difference in flavour between Robusta and Arabica coffee. l‐Leucine was selected as an additive based on the Maillard reaction. The pre‐treatment method conducted in this study was a short soaking (M1) or spraying procedure (M2), then LP was added at varying levels up to 3% (w/w, 30 g kg−1). All samples were roasted (240 °C for 15 min) and extracted using an espresso machine. Volatile compounds were analysed by solid‐phase microextraction‐gas chromatography‐mass selective detection.RESULTSThirty volatile compounds (six pyrroles, eight pyrazines, three phenols, nine furans, two ketones, two aldehydes) were analysed. In 15 coffee samples, the levels of total volatile compounds (based on peak area ratios) ranged from 8.9 (M1‐1) to 15. Non‐treated Robusta had higher levels of bitter aroma compounds than Arabica coffee, and Robusta coffee had lower levels of bitter aroma compounds when pre‐treated with LP. The sum of bitter volatiles (phenols, pyrroles, pyrazines) was lowest in M1‐5 (3% LP), M2‐1 (1% LP; both dried at 50 °C for 15 min) and M2‐7 (3% LP, dried at 70 °C for 15 min) compared with non‐treated Robusta (P < 0.05).CONCLUSIONFrom the results of this study it can be shown that pre‐treatment with LP can improve the flavour of Robusta. © 2023 Society of Chemical Industry.
Why disability data capture is key to improving inclusion outcomes in scholarly publishing
Authors: Holt Simon , Hunter Sylvia , Osborne‐Martin Erin , Scott Stacy 
Published: February 2023

Key points
Explains why mass disability data capture is potentially transformative for the scholarly publishing industry.
Considers major challenges, particularly focusing on cultural and systemic roadblocks.
Offers practical suggestions for a framework, using the accessibility movement as a case study.
Optical Vortex Brillouin Laser
Authors: Zeng Xinglin , Russell Philip St. J. , Chen Yang , Wang Zheqi , Wong Gordon K. L. , Roth Paul , Frosz Michael H. , Stiller Birgit 
Published: February 2023

AbstractOptical vortices, which have been extensively studied over the last decades, offer an additional degree of freedom useful in many applications, such as optical tweezers and quantum control. Stimulated Brillouin scattering (SBS), providing a narrow linewidth and a strong nonlinear response, has been used to realize quasi‐continuous wave lasers. Here, stable oscillation of optical vortices and acoustic modes in a Brillouin laser based on chiral photonic crystal fiber (PCF) is reported, which robustly supports helical Bloch modes (HBMs) that carry circularly polarized optical vortex and display circular birefringence. A narrow‐linewidth Brillouin fiber laser that stably emits 1st‐ and 2nd‐order vortex‐carrying HBMs is implemented. Angular momentum conservation selection rules dictate that pump and backward Brillouin signals have opposite topological charge and spin. Additionally, it is shown that when the chiral PCF is placed within a laser ring cavity, the linewidth‐narrowing associated with lasing permits the peak of the Brillouin gain that corresponds to acoustic mode to be measured with resolution of 10 kHz and accuracy of 520 kHz. The results pave the way to a new generation of vortex‐carrying SBS systems with applications in optical tweezers, quantum information processing, and vortex‐carrying nonreciprocal systems.
Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case–Control Study
Authors: Cilia Roberto , Cereda Emanuele , Piatti Marco , Pilotto Andrea , Magistrelli Luca , Golfrè Andreasi Nico , Bonvegna Salvatore , Contaldi Elena , Mancini Francesca , Imbalzano Gabriele , De Micco Rosa , Colucci Fabiana , Braccia Arianna , Bellini Gabriele , Brovelli Francesco , Zangaglia Roberta , Lazzeri Giulia , Russillo Maria Claudia , Olivola Enrica , Sorbera Chiara , Cereda Viviana , Pinto Patrizia , Sucapane Patrizia , Gelosa Giorgio , Meloni Mario , Pistoia Francesca , Sessa Maria , Canesi Margherita , Modugno Nicola , Pacchetti Claudio , Brighina Laura , Pellecchia Maria Teresa , Ceravolo Roberto , Sensi Mariachiara , Zibetti Maurizio , Comi Cristoforo , Padovani Alessandro , Zecchinelli Anna L. , Di Fonzo Alessio , Tessitore Alessandro , Morgante Francesca , Eleopra Roberto 
Published: February 2023

AbstractBackgroundEffects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO‐B inhibitors (iMAO‐B) safinamide and rasagiline are still based on empirical approaches.ObjectivesTo estimate LED of safinamide 50 and 100 mg.MethodsIn this multicenter, longitudinal, case–control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N = 130), safinamide 50 mg (N = 144), or rasagiline 1 mg (N = 97) for 9 ± 3 months and a control group of patients never treated with any iMAO‐B (N = 129).ResultsMajor baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS‐II scores and Levodopa dose than control subjects. After a mean follow‐up of 8.8‐to‐10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS‐III and OFF‐related UPDRS‐IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO‐B groups. After adjusting for age, disease duration, duration of follow‐up, baseline values and taking change in UPDRS‐III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1 mg equally corresponded to 100 mg LED.ConclusionsWe used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.
Phantom Boarder Relates to Experimentally‐Induced Presence Hallucinations in Parkinson's Disease
Authors: Blanke Olaf , Bernasconi Fosco , Potheegadoo Jevita 
Published: February 2023

AbstractBackgroundPhantom boarder (PB) is the sensation that someone uninvited is in the patient's home despite evidence to the contrary. It is mostly reported by patients with neurodegenerative disorders such as Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease (PD). Presence hallucination (PH) is frequent in neurodegenerative disease, shares several aspects with PB, and is the sensation that someone is nearby, behind or next to the patient (when nobody is actually there). Recent work developed a sensorimotor method to robotically induce PH (robot‐induced PH, riPH) and demonstrated that a subgroup of PD patients showed abnormal sensitivity for riPH.ObjectiveWe investigated if PD patients with PB (PD‐PB) would (1) show elevated sensitivity for riPH that (2) is comparable to that of patients reporting PH, but not PB (PD‐PH).MethodsWe studied the sensitivity of non‐demented PD patients in a sensorimotor stimulation paradigm, during which three groups of patients (PD‐PB; PD‐PH; PD patients without hallucinations, PD‐nPH) were exposed to different conditions of conflicting sensorimotor stimulation.ResultsWe show that PD‐PB and PD‐PH groups had a higher sensitivity to riPH (compared to PD‐nPH). PD‐PB and PD‐PH groups did not differ in riPH sensitivity. Together with interview data, these behavioral data on riPH show that PB is associated with PH, suggesting that both share some underlying brain mechanisms, although interview data also revealed phenomenological differences.ConclusionsBecause PD‐PB patients did not suffer from dementia nor delusions, we argue that these shared mechanisms are of perceptual‐hallucinatory nature, involving sensorimotor signals and their integration.
An RF coil design to enable quintuple nuclear whole‐brain MRI
Authors: Dai Jiying , Gosselink Mark , van der Velden Tijl Antonius , Meliadò Ettore Flavio , Raaijmakers Alexander Jan Eberhard , Klomp Dennis Wilhelmus Johannes 
Published: February 2023

PurposeTo bring metabolic imaging based on multi‐NMR toward practical use from the RF hardware perspective.MethodsA highly integrated RF coil is designed for whole‐brain MRI and MRS targeted to five nuclear species: 1H, 19F, 31P, 23Na, and 13C. Dipole antennas and closely loaded local receiver loops are combined in this setup.ResultsHigh‐quality in vivo scan results of 1H, 31P, 23Na, and 13C on healthy volunteers have been achieved. For 1H, the transmit efficiency is 77% of a single‐tuned commercial head coil (NOVA 8‐transmit [Tx]/32‐receive [Rx]; NOVA Medical, Wilmington, MA, USA). For 31P, 110% SNR of a dual‐tuned close‐fit head‐birdcage was achieved at the center of the subject, based on MR experiments on a phantom. For 31P, 23Na, and 13C, bench measurements indicate SNR loss of 15%, 27%, and 30% compared with single‐tuned conditions. 19F performance has been proven to be similar to that of 1H through bench tests and electromagnetic simulations.ConclusionWith this device, 1H‐based anatomic images that are expected to meet clinical requirements, as well as high‐quality multi‐NMR images and spectra, can be acquired within one scan session without hardware replacement or patient repositioning, enabling morphologic and metabolic MRI within acceptable scan time.
Motion compensated self supervised deep learning for highly accelerated 3D ultrashort Echo time pulmonary MRI
Authors: Miller Zachary , Johnson Kevin M. 
Published: February 2023

PurposeTo investigate motion compensated, self‐supervised, model based deep learning (MBDL) as a method to reconstruct free breathing, 3D pulmonary UTE acquisitions.Theory and MethodsA self‐supervised eXtra dimension MBDL architecture (XD‐MBDL) was developed that combined respiratory states to reconstruct a single high‐quality 3D image. Non‐rigid motion fields were incorporated into this architecture by estimating motion fields from a lower resolution motion resolved (XD‐GRASP) reconstruction. Motion compensated XD‐MBDL was evaluated on lung UTE datasets with and without contrast and compared to constrained reconstructions and variants of self‐supervised MBDL that do not account for dynamic respiratory states or leverage motion correction.ResultsImages reconstructed using XD‐MBDL demonstrate improved image quality as measured by apparent SNR (aSNR), contrast to noise ratio (CNR), and visual assessment relative to self‐supervised MBDL approaches that do not account for dynamic respiratory states, XD‐GRASP and a recently proposed motion compensated iterative reconstruction strategy (iMoCo). Additionally, XD‐MBDL reduced reconstruction time relative to both XD‐GRASP and iMoCo.ConclusionA method was developed to allow self‐supervised MBDL to combine multiple respiratory states to reconstruct a single image. This method was combined with graphics processing unit (GPU)‐based image registration to further improve reconstruction quality. This approach showed promising results reconstructing a user‐selected respiratory phase from free breathing 3D pulmonary UTE acquisitions.
In vivo reproducibility of 3D relayed NOE in the healthy human brain at 7 T
Authors: Benyard Blake , Nanga Ravi Prakash Reddy , Wilson Neil E. , Thakuri Deepa , Jacobs Paul S. , Swain Anshuman , Kumar Dushyant , Reddy Ravinder 
Published: February 2023

PurposeNuclear Overhauser effect (NOE) is based on dipolar cross‐relaxation mechanism that enables the indirect detection of aliphatic protons via the water proton signal. This work focuses on determining the reproducibility of NOE magnetization transfer ratio (NOEMTR) and isolated or relayed NOE (rNOE) contributions to the NOE MRI of the healthy human brain at 7 Tesla (T).MethodsWe optimized the amplitude and length of the saturation pulse by acquiring NOE images with different values with multiple saturation lengths. Repeated NOE MRI measurements were made on five healthy volunteers by using optimized saturation pulse parameters including correction of B0 and inhomogeneities. To isolate the individual contributions from z‐spectra, we have fit the NOE z‐spectra using multiple Lorentzians and calculated the total contribution from each pool contributing to the overall NOEMTR contrast.ResultsWe found that a saturation amplitude of 0.72 μT and a length of 3 s provided the highest contrast. We found that the mean NOEMTR value in gray matter (GM) was 26%, and in white matter (WM) was 33.3% across the 3D slab of the brain. The mean rNOE contributions from GM and WM values were 8.9% and 9.6%, which were ∼10% of the corresponding total NOEMTR signal. The intersubject coefficient of variations (CoVs) of NOEMTR from GM and WM were 4.5% and 6.5%, respectively, whereas the CoVs of rNOE were 4.8% and 5.6%, respectively. The intrasubject CoVs of the NOEMTR range was 2.1%–4.2%, and rNOE range was 2.9%–10.5%.ConclusionThis work has demonstrated an excellent reproducibility of both inter‐ and intrasubject NOEMTR and rNOE metrics in healthy human brains at 7 T.