bluuebunny/crossref_metadata_2025 huggingface dataset:
Errors in Conventional and Input‐Output—based Life—Cycle Inventories
Authors: Lenzen Manfred
Published: July 2002

Conventional process‐analysis‐type techniques for compiling life‐cycle inventories suffer from a truncation error, which is caused by the omission of resource requirements or pollutant releases of higher‐order upstream stages of the production process. The magnitude of this truncation error varies with the type of product or process considered, but can be on the order of 50%. One way to avoid such significant errors is to incorporate input‐output analysis into the assessment framework, resulting in a hybrid life‐cycle inventory method. Using Monte‐Carlo simulations, it can be shown that uncertainties of input‐output– based life‐cycle assessments are often lower than truncation errors in even extensive, third‐order process analyses.
RE-EXAMINING THE WARNING OF ECCL. XII 12
Authors:   Shields
Published: July 2002

This article argues that the imperative "be warned" in Eccl. xii 12 should not be read as part of the opening clause, but rather as part of the subsequent clauses which thus become specific warnings against the tasks which occupied the sages of Qohelet's time.
Taxonomic status of Trapelus ruderatus (Olivier) and T. persicus (Blanford), and validity of T. lessonae (De Filippi)
Authors: Rastegar-Pouyani Nasrullah
Published: July 2002

The systematic status of the ground agamids (conventional) Trapelus ruderatus and Trapelus persicus is re-evaluated based on material collected by the author on the Iranian Plateau and material from various museum collections, including the type specimens of Trapelus ruderatus (Olivier), T. megalonyx Günther, T. lessonae (De Filippi), T. persicus (Blanford) and T. ruderatus baluchianus (Smith). In conclusion, the holotype of Trapelus ruderatus is a subadult (conventional) T. persicus and that of T. lessonae is a typical (conventional) T. ruderatus ruderatus. Furthermore, T. megalonyx is a well-established species and T. r. baluchianus is not a valid taxonomic entity, being a junior synonym of T. megalonyx. So, some major nomenclatural changes are inevitable: Since T. lessonae is the oldest available name, it is revived for all populations of the (conventional) T. r. ruderatus, and the specific name “ruderatus” is, in turn, assigned for all populations of the (conventional) T. persicus (because of priority). Thus, the specific name “persicus” comes under the synonymy of “ruderatus” and is no longer available.
Comparative studies on hemipenes of four species of Trimeresurus (sensu stricto) (Serpentes: Crotalinae)
Authors: Fuji Zhang , Peng Guo
Published: July 2002

The hemipenes of four species of Chinese pit vipers, Trimeresurus albolabris, T. medoensis, T. stejnegeri, T. xiangchengensis, were described and illustrated. The results showed that the four species are notably different in hemipenial structures, and the hemipenes of four species can be clustered into three types. Furthermore, a comparison with the hemipenes of related species in the genus was conducted.
MALE-MALE COMPETITION AND INTERSEXUAL INTERACTIONS IN UNDERGROUND MATING OF THE FIDDLER CRAB UCA PARADUSSUMIERI
Authors: Koga Tsunenori , Murai Minoru , Yong Hoi-Sen
Published: July 2002

We investigated inter-male competition for female mates and intersexual interactions in underground mating (UM) of the fiddler crab Uca paradussumieri . Males search for and then enter the burrows of females that are ready to ovulate ('pre-ovigerous'). In order to ensure their paternity, these males guard the female until she ovulates the following day. Thereafter the male leaves. Intruding male conspecifics attempt to reach the female. Guarding males either fight with them (N = 27), or use the flat-claw defence (N = 96) in which the male stands in the burrow shaft and blocks the entrance with his enlarged claw. The flat-claw was a very successful defence tactic (93% success), even when the intruder was larger than the guarding male. Pre-ovigerous females accepted the first male to enter her burrow, suggesting that female mate choice does not occur. Though males that succeeded to enter the burrow of pre-ovigerous female were larger than males that failed to do so, males that succeeded UM were not larger than males that failed UM. Males that succeeded UM by a take-over were not larger than either the males that were defeated or the males that succeeded in UM after their first entering. Early localization of pre-ovigerous females was important in male mating success, as was a male's ability to defend the female before she ovulated. However, some females that were not pre-ovigerous were guarded forcibly for 2 days by males that had failed to pair with a pre-ovigerous female that day. Prolonged guarding was less successful for males than guarding for one day, probably because the males had to fight with more intruders. In addition, prolonged guarding may not be adaptive for females because they lose feeding time and mate with males that lack competitive abilities.
Distribution pattern and mortality of the white tip nematode, Aphelenchoides besseyi (Nematoda: Aphelenchoididae), among rice seeds
Authors: Togashi Katsumi , Hoshino Shigeru
Published: July 2002

Aphelenchoides besseyi is a seed-borne nematode and the causal agent of rice white tip disease. To determine the relationships between nematode numbers per seed, size of seed harbouring nematodes, and nematode mortality, 18 panicles were collected from 12 paddy fields showing three different levels of white tip disease. The panicles were investigated after storage for 30-82 days at 4°C. There was no nematode mortality within seeds during storage. Mean nematode number per seed increased and mean degree of seed swelling decreased as the paddy field infestation of white tip disease increased. For paddy field means, there was a significant, negative correlation between the mean nematode number per seed and the mean degree of rice seed swelling. Intriguingly, for individual seeds, the mean degree of swelling increased up to that typical of well-developed seeds with increasing nematode number per seed. Nematode mortality occurred in an inversely density-dependent fashion within individual seeds. The nematode exhibited a clumped distribution among seeds in each paddy field. Such ecological features of the nematode might contribute to its persistence in rice plant population.
Effects of temperature on stem nematode (Ditylenchus dipsaci) infestation of white clover (Trifolium repens) swards
Authors: Griffith Gwyn S. , Cook Roger , Mizen K. Anthony
Published: July 2002

Development of stem nematode (Ditylenchus dipsaci) infestations of white
clover (Trifolium repens) in artificially established swards and
transplanted turfs was monitored at field sites with different mean daily
temperatures. In artificial swards the level of nematode infestation was
inversely related to mean daily temperature. In transplanted turfs,
nematodes caused a 46% reduction in white clover density over an 18-month
period; the level of damage was not significantly affected by mean daily
temperature although the proportion of clover stolons infested was higher at
colder temperatures. Reductions in infestation levels at higher temperatures
are probably the result of reduced survival in soil and the upper lethal
temperature for nematodes being exceeded more frequently under warmer
conditions. Influence de la temperature sur l'infestation, dans des
pelouses, du trefle blanc (Trifolium repens) par le nematode des tiges
(Ditylenchus dipsaci) - Le developpement de l'infestation du trefle blanc
(Trifolium repens) par le nematode des tiges (Ditylenchus dipsaci) dans des
pelouses artificielles ou des gazons transplantes a ete controlee, au champ,
a differentes temperatures journalieres. Dans les pelouses artificielles, le
niveau de l'infestation par le nematode est inversement proportionnel a la
temperature journaliere moyenne. Dans le cas des gazons transplantes, et sur
une periode de 18 mois, les nematodes reduisent de 46% la densite des
trefles blancs; le niveau des degats n'est pas significativement affecte par
la temperature moyenne journaliere quoique la proportion de stolons de
trefle infestes soit plus elevee aux temperatures les plus basses. La
diminution de l'infestation aux temperatures elevees est probablement due a
une moindre survie du nematode dans le sol et au fait que les temperatures
letales pour lui soient plus frequemment depassees dans des conditions de
plus grande chaleur.
The effect of low temperature on preparasitic juveniles of Romanomermis (Nematoda: Mermithidae)
Authors: Peng Yufang , Song Yi , Song Jinzhang , Platzer Edward G.
Published: July 2002

This study showed that at low temperatures (-2 to 2C), more than 90% of the
preparasitic juveniles of Romanomermis yunanensis and Romanomermis sp.
survived for 8 and 5 days, respectively, but at 26 to 28 C and 16 to 18 C,
the 90% survival time for preparasites of these species was 24 and 48 h,
respectively. The percentage of mosquitoes infected by preparasites of R.
yunanensis maintained at low temperature for 8-11 days was 87.5-94.3%.
Preparasites of Romanomermis sp. maintained for 5 days at low temperature
infected 81.5 and 55.1% of the mosquitoes in the laboratory and field tests,
respectively. This infectivities were not significantly different (P >
0.05) from the pre-storage values. This data indicates that low temperature
storage prolonged the survival time and had no effect on the infectivity of
the preparasitic juveniles of these Romanomermis species. Effet de basses
temperatures sur les juveniles infestants de Romanomermis (Nematoda:
Mermithidae)- La presente etude montre qu'a basse temperature (de- 2 a + 2
C) plus de 90% des juveniles preparasites de Romanomermis yunanensis et
Romanomermis sp. survivent, respectivement, 8 et 5 jours tandis qu'entre 26
et 28 C ou 16 et 18 C leur survie n'est que de 24 et 48 h, respectivement.
Le pourcentage des moustiques infestes par les juveniles preparasites de R.
vunanensis maintenus a basse temperature pendant 8 a 11 jours variait de
87,5 a 94,3%. Les juveniles preparasites de Romanomermis sp. maintenus 5
jours a basse temperature infestent 81,5% de moustiques lors de tests au
laboratoire et 55,1% lors de tests au champ. Ces taux d'infestivite ne sont
pas significativement differents (P > 0 . 05) de ceux releves avant
stockage. Ces donnees indiquent que le stockage a basse temperature prolonge
le temps de survie des juveniles preparasites de ces especes de Romanomermis
et n'a aucun effet sur leur infestivite.
Authigenic kaolin and illitic minerals during burial diagenesis of sandstones: a review
Authors: Lanson B. , Beaufort D. , Berger G. , Bauer A. , Cassagnabère A. , Meunier A.
Published: July 2002

The diagenetic evolution of kaolin and illitic minerals in sandstones is described here. The structural characterization of these minerals, the possible reaction pathways leading to their crystallization, and the origin of the fluids involved are discussed specifically.

While early precipitation of kaolinite is in general related to flushing by meteoric waters, subsequent diagenetic kaolinite-to-dickite transformation probably results from invasion by acidic fluids of organic origin. Dickite is the stable polytype in most sandstone formations and the kaoliniteto- dickite conversion is kinetically controlled.

The conventional model of kaolin illitization, assuming a thermodynamic control in a closed system, is discussed and compared to an alternative model in which illitization of kaolin is not coupled to dissolution of K-feldspar (Bergeret al., 1997). In the latter model, illite crystallization at the expense of kaolin implies that an energy barrier is overcome either by an increased K+/H+activity ratio in solution or by a considerable temperature increase.
Ligation of CD11b and CD11c β2 integrins by antibodies or soluble CD23 induces macrophage inflammatory protein 1α (MIP-1α) and MIP-1β production in primary human monocytes through a pathway dependent on nuclear factor–κB
Authors: Rezzonico Roger , Imbert Veronique , Chicheportiche Rachel , Dayer Jean-Michel
Published: July 2002

Chemokines and adhesion molecules such as integrins play a major part in the trafficking, extravasation, and recruitment of leukocytes to inflammatory sites. This study investigated the effects of β2 integrin engagement on chemokine production by freshly isolated human monocytes. We found that ligation of CD11b or CD11c but not CD11a α chains of β2 integrins by antibodies or soluble CD23 (sCD23) fusion proteins rapidly induced transcription and secretion of interleukin 8, macrophage inflammatory protein (MIP) 1α, and MIP-1β. Because the promoters of these chemokine genes contain κB binding sites, we assessed the possible role of nuclear factor–κB (NF-κB) in controlling induction of the genes through β2 integrin engagement. Electrophoretic mobility shift assays showed that sCD23 or antibodies to CD11b or to CD11c up-regulated DNA-binding activity of NF-κB. Activation of NF-κB was accompanied by degradation of its cytosolic inhibitor IκB-α. Blockade of depletion of IκB-α by proteasome inhibitors (proteasome inhibitor I or acetyl-leucinyl-leucinyl-norleucinal) led to concomitant inhibition of NF-κB DNA-binding activity and expression of MIP-1α and MIP-1β messenger RNA induced by β2 integrin ligation. These results suggest that triggering of CD11b or CD11c β2 integrin on primary human monocytes provides activation signals leading to nuclear translocation of NF-κB and subsequent secretion of MIP-1α and MIP-1β that may have an important role in recruitment of other inflammatory cells during initiation of an inflammatory response.
Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset
Authors: Cooper Megan A. , Fehniger Todd A. , Turner Sarah C. , Chen Kenneth S. , Ghaheri Bobak A. , Ghayur Tariq , Carson William E. , Caligiuri Michael A.
Published: July 2002

During the innate immune response to infection, monocyte-derived cytokines (monokines), stimulate natural killer (NK) cells to produce immunoregulatory cytokines that are important to the host's early defense. Human NK cell subsets can be distinguished by CD56 surface density expression (ie, CD56bright and CD56dim). In this report, it is shown that CD56bright NK cells produce significantly greater levels of interferon-γ, tumor necrosis factor-β, granulocyte macrophage–colony-stimulating factor, IL-10, and IL-13 protein in response to monokine stimulation than do CD56dim NK cells, which produce negligible amounts of these cytokines. Further, qualitative differences in CD56bright NK-derived cytokines are shown to be dependent on the specific monokines present. For example, the monokine IL-15 appears to be required for type 2 cytokine production by CD56bright NK cells. It is proposed that human CD56bright NK cells have a unique functional role in the innate immune response as the primary source of NK cell–derived immunoregulatory cytokines, regulated in part by differential monokine production.
Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT
Authors: van Esser Joost W. J. , van der Holt Bronno , Meijer Ellen , Niesters Hubert G. M. , Trenschel Rudolf , Thijsen Steven F. T. , van Loon Anton M. , Frassoni Francesco , Bacigalupo Andrea , Schaefer Ulrich W. , Osterhaus Albert D. M. E. , Gratama Jan Willem , Löwenberg Bob , Verdonck Leo F. , Cornelissen Jan J.
Published: July 2002

Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and sequelae of EBV reactivation following allo-SCT. EBV reactivation was retrospectively monitored in 85 EBV-seropositive recipients of a T-cell–depleted (TCD) allo-SCT and 65 EBV-seropositive recipients of an unmanipulated allo-SCT. Viral reactivation (more than 50 EBV genome equivalents [gEq]/mL) was monitored frequently by quantitative real-time plasma polymerase chain reaction until day 180 after SCT. Probabilities of developing viral reactivation were high after both unmanipulated and TCD-allogeneic SCT (31% ± 6% versus 65% ± 7%, respectively). A high CD34+ cell number of the graft appeared as a novel significant predictor (P = .001) for EBV reactivation. Recurrent reactivation was observed more frequently in recipients of a TCD graft, and EBV-LPD occurred only after TCD-SCT. High-risk status, TCD, and use of antithymocyte globulin were predictive for developing EBV-LPD. Plasma EBV DNA quantitatively predicted EBV-LPD. The positive and negative predictive values of a viral load of 1000 gEq/mL were, respectively, 39% and 100% after TCD. Treatment-related mortality did not differ significantly between TCD and non-TCD transplants, but the incidence of chronic graft-versus-host disease was significantly less in TCD patients. It is concluded that EBV reactivation occurs frequently after TCD and unmanipulated allo-SCT, especially in recipients of grafts with high CD34+ cell counts. EBV-LPD, however, occurred only after TCD, and EBV load quantitatively predicted EBV-LPD in recipients of a TCD graft.
Cellular stress response and apoptosis in cancer therapy
Authors: Herr Ingrid , Debatin Klaus-Michael
Published: July 2002

Anticancer treatment using cytotoxic drugs is considered to mediate cell death by activating key elements of the apoptosis program and the cellular stress response. While proteolytic enzymes (caspases) serve as main effectors of apoptosis, the mechanisms involved in activation of the caspase system are less clear. Two distinct pathways upstream of the caspase cascade have been identified. Death receptors, eg, CD95 (APO-1/Fas), trigger caspase-8, and mitochondria release apoptogenic factors (cytochrome c, Apaf-1, AIF), leading to the activation of caspase-9. The stressed endoplasmic reticulum (ER) contributes to apoptosis by the unfolded protein response pathway, which induces ER chaperones, and by the ER overload response pathway, which produces cytokines via nuclear factor-κB. Multiple other stress-inducible molecules, such as p53, JNK, AP-1, NF-κB, PKC/MAPK/ERK, and members of the sphingomyelin pathway have a profound influence on apoptosis. Understanding the complex interaction between different cellular programs provides insights into sensitivity or resistance of tumor cells and identifies molecular targets for rational therapeutic intervention strategies.
Spontaneous interleukin-5 production in cutaneous T-cell lymphoma lines is mediated by constitutively activated Stat3
Authors: Nielsen Mette , Nissen Mogens H. , Gerwien Jens , Zocca Mai-Britt , Rasmussen Helene M. , Nakajima Koichi , Röpke Carsten , Geisler Carsten , Kaltoft Keld , Ødum Niels
Published: July 2002

Mycosis fungoides is a low-grade cutanous T-cell lymphoma (CTCL) of unknown etiology. In advanced stages of CTCL, a shift in cytokine profile from TH1 to TH2 is observed, which coincides with eosinophilia, high levels of immunoglobulin E, and increased susceptibility to bacterial infections. It is, however, unknown why TH2 cytokines predominate in advanced CTCL, and the cellular source of these cytokines also remains to be identified. In several leukemias and lymphomas, constitutively activated signal transducer and activator of transcription (Stat) signaling pathways have been detected. In a previous study, constitutive activation of Stat3 was found in tumor cells isolated from affected skin and blood from CTCL patients. Here, it is shown that CTCL tumor cell lines, but not nonmalignant cell lines, spontaneously produce interleukin-5 (IL-5), IL-6, and IL-13. Transfection of tumor cells with dominant-negative Stat3 almost completely blocks IL-5 production and strongly inhibits IL-13 production, whereas IL-6 production is unaffected. Thus, the data show that malignant CTCL cells themselves might contribute to the change in cytokine pattern accompanying progression of CTCL. In conclusion, constitutively activated Stat3 is found to mediate a spontaneous IL-5 production and regulate IL-13 production in CTCL cell lines, pointing toward a new role of Stat3 in malignant transformation.
Randomized Controlled Trial of Yttrium-90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell Non-Hodgkin’s Lymphoma
Authors: Witzig Thomas E. , Gordon Leo I. , Cabanillas Fernando , Czuczman Myron S. , Emmanouilides Christos , Joyce Robin , Pohlman Brad L. , Bartlett Nancy L. , Wiseman Gregory A. , Padre Norman , Grillo-López Antonio J. , Multani Pratik , White Christine A.
Published: July 2002

PURPOSE: Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin’s lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 (90Y) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20+transformed NHL.

PATIENTS AND METHODS: Patients received either a single intravenous (IV) dose of90Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m2IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m2) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel.

RESULTS: ORR was 80% for the90Y ibritumomab tiuxetan group versus 56% for the rituximab group (P = .002). Complete response (CR) rates were 30% and 16% in the90Y ibritumomab tiuxetan and rituximab groups, respectively (P = .04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the90Y ibritumomab tiuxetan group versus 12.1 months in the control group (P = .6), and time to progression was 11.2 versus 10.1 months (P = .173) in all patients. Durable responses of ≥ 6 months were 64% versus 47% (P = .030). Reversible myelosuppression was the primary toxicity noted with90Y ibritumomab tiuxetan.

CONCLUSION: Radioimmunotherapy with90Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.
Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor in Patients Hospitalized With Heart Failure With Mildly Reduced or Preserved Ejection Fraction
Authors: Abdel Jawad Mohammad , Spertus John A. , Ikeaba Uchechukwu , Greene Stephen J. , Fonarow Gregg C. , Chiswell Karen , Chan Paul S.
Published: November 2024

Importance

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are the first therapy shown to improve clinical outcomes for patients with heart failure (HF) and a left ventricular ejection fraction (LVEF) greater than 40%. Nationwide adoption of SGLT2is in the US since publication of the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved) in August 2021 is unknown.

Objective

To examine trends and hospital-level variation in SGLT2i adoption.

Design, Setting, and Participants

This cohort study included patients with LVEF greater than 40% who were hospitalized for decompensated HF at 1 of 557 sites in the US between July 1, 2021, and September 30, 2023, from the Get With The Guidelines–Heart Failure registry.

Main Outcomes and Measures

Patient-level trends and site-level variation in prescription rates of SGLT2i at hospital discharge. Site-level variation was quantified using the median odds ratio, which describes the average odds that a patient being treated at one vs another randomly selected hospital would receive SGLT2i therapy at discharge.

Results

Of 158 849 patients (median [IQR] age, 76 [66-85] years; 89 816 females [56.5%]), 22 126 eligible patients (13.9%) with HF and an LVEF greater than 40% were prescribed an SGLT2i at hospital discharge. Quarterly prescription rates increased from 4.2% in July to September 2021 to 23.5% in July to September 2023 (P for trend < .001). SGLT2i prescription was more likely among patients with HF with mildly reduced LVEF (41%-49%) than in those with preserved LVEF (≥50%; 5127 of 27 712 patients [18.5%] vs 16 999 of 131 137 patients [13.0%]; absolute standardized difference, 16.7%). After adjustment for patient characteristics, there was a high variance between hospitals in the rate of SGLT2i prescription (median odds ratio, 2.12; 95% CI, 2.02-2.25). Among 518 hospitals with 10 or more eligible discharges, 11 hospitals (2.1%) discharged 50% or more of their patients with an SGLT2i prescription, while 232 (44.8%) discharged fewer than 10% of eligible patients with an SGLT2i prescription.

Conclusion and Relevance

For patients with HF and an LVEF greater than 40%, discharge prescription of SGLT2is increased from 4.2% to 23.5% during the first 2 years after the EMPEROR-Preserved trial demonstrating treatment benefits; however, these rates varied across US hospitals.
Antidiabetic Medication and Asthma Attacks
Authors: Lee Bohee , Man Kenneth K. C. , Wong Ernie , Tan Tricia , Sheikh Aziz , Bloom Chloe I.
Published: November 2024

Importance

Elevated body mass index (BMI) and type 2 diabetes are prevalent in asthma and are associated with an increase in the risk of asthma attacks. In experimental studies, the diabetes medications metformin and glucagon-like peptide-1 receptor agonists (GLP-1RA) have mitigated airway inflammation, hyperresponsiveness, and remodeling. However, epidemiological evidence is limited.

Objective

To estimate the association of metformin and add-on antidiabetic medications (GLP-1RA, dipeptidyl peptidase-4 inhibitors, sulphonylureas, sodium-glucose cotransporter-2 inhibitors, and insulin) with asthma attacks.

Design, Setting, and Participants

The study used data from the UK Clinical Practice Research Datalink (CPRD) Aurum linked hospital admissions and mortality data from 2004 to 2020. A triangulation approach was used that applied 2 distinct approaches to enhance robustness: a self-controlled case series (SCCS) and a metformin new user cohort with inverse probability of treatment weighting (IPTW). Eligible participants were new users of metformin with type 2 diabetes. To evaluate the association between metabolic phenotypes (BMI, glycemic control) and asthma phenotypes (type 2 inflammation, asthma severity), interaction analyses were conducted. Negative control analyses were conducted to assess for bias.

Exposure

The primary exposure was metformin; secondary exposures included add-on antidiabetic medications.

Main Outcomes

The primary outcome was first asthma exacerbation (short course of oral corticosteroids, unscheduled asthma-related hospital attendance, or death) during 12-month follow-up. Incidence rate ratios (IRRs) with 95% CIs were estimated using fixed-effect conditional Poisson models in the SCCS, and hazard ratios (HRs) were estimated using weighted Cox proportional hazards models in the cohort.

Results

Of more than 2 million adults with asthma, 4278 patients (2617 women [61.2%]; mean [SD] age, 52.9 [13.6] years) were identified for the SCCS and 8424 patients (4690 women [55.7%]; unexposed: mean [SD] age, 61.6 [13.2] years; exposed: mean [SD] age, 59.7 [13.7] years) for the IPTW cohort. Metformin was found to be associated with fewer asthma attacks of similar magnitude in both approaches (SCCS: IRR, 0.68; 95% CI, 0.62-0.75; IPTW: HR, 0.76; 95% CI, 0.67-0.85). Negative control analyses did not find evidence of significant bias. Hemoglobin A1c levels, BMI, blood eosinophil cell counts, and asthma severity did not modify the association. The only add-on antidiabetic medication to have an additive association was GLP-1RA (SCCS: IRR, 0.60; 95% CI, 0.49-0.73).

Conclusions and Relevance

The results of this cohort study suggest that metformin was associated with a lower rate of asthma attacks, with further reductions with the use of GLP-1RA. This appeared to be associated with mechanisms other than through glycemic control or weight loss and occurred across asthma phenotypes.
Next-Generation Multitarget Stool DNA vs Fecal Immunochemical Test in Colorectal Cancer Screening
Authors: Seum Teresa , Niedermaier Tobias , Heisser Thomas , Hoffmeister Michael , Brenner Hermann
Published: November 2024

This diagnostic study compares the specificity and sensitivity of comercial fecal immunochemical tests with a multitarget stool DNA test.
Systemic Postnatal Corticosteroids, Bronchopulmonary Dysplasia, and Survival Free of Cerebral Palsy
Authors: Doyle Lex W. , Mainzer Rheanna , Cheong Jeanie L. Y.
Published: November 2024

Importance

Systemic postnatal corticosteroids have been shown to reduce rates of bronchopulmonary dysplasia (BPD) in infants born preterm, but both corticosteroids and BPD are associated with cerebral palsy.

Objective

To describe how the association between systemic postnatal corticosteroids and survival free of cerebral palsy varies with the risk of BPD in infants born preterm, and if the association differs between dexamethasone and hydrocortisone, or with age at starting treatment.

Design, Setting, and Participants

This comparative effectiveness research used weighted meta-regression analysis of eligible randomized clinical trials (RCTs) of systemic postnatal corticosteroids reported from June 1989 through March 2022 that included rates of all of BPD, mortality, and cerebral palsy in neonatal intensive care units in 10 countries. Infants born preterm at risk of BPD were included. Data were analyzed from April and July 2024.

Interventions

Systemic dexamethasone or hydrocortisone.

Main Outcomes and Measures

Type and timing of corticosteroid, control group rate of BPD, and risk difference in survival free of cerebral palsy between corticosteroid and control arms.

Results

Twenty-six RCTs with data on 3700 randomized infants were eligible; 18 (69%) investigated dexamethasone and 8 (31%) hydrocortisone; 12 (46%) started treatment in the first week after birth. There was evidence for a differential association of the type of corticosteroid with the effect of systemic dexamethasone on survival free of cerebral palsy and the risk of BPD in control groups (interaction coefficient, 0.54; 95% CI, 0.25-0.82; P = .001). For dexamethasone, for every 10–percentage point increase in the risk of BPD, the risk difference for survival free of cerebral palsy increased by 3.74% (95% CI, 1.54 to 5.93; P = .002). Dexamethasone was associated with improved survival free of cerebral palsy at a risk of BPD greater than 70%. Conversely, dexamethasone was associated with harm at a risk of BPD less than 30%. There was some evidence for a negative association with hydrocortisone, with possible benefit with risk of BPD less than 30%. There was no strong evidence for a differential effect of timing among those treated with dexamethasone (interaction coefficient, 0.13; 95% CI, −0.04 to 0.30; P = .14).

Conclusions and Relevance

The findings suggest that dexamethasone (compared with control) was associated with improved rates of survival free of cerebral palsy in infants at high risk of BPD but should be avoided in those at low risk. A role for hydrocortisone is uncertain.
Machine learning in image‐based outcome prediction after radiotherapy: A review
Authors: Yuan Xiaohan , Ma Chaoqiong , Hu Mingzhe , Qiu Richard L. J. , Salari Elahheh , Martini Reema , Yang Xiaofeng
Published: November 2024

The integration of machine learning (ML) with radiotherapy has emerged as a pivotal innovation in outcome prediction, bringing novel insights amid unique challenges. This review comprehensively examines the current scope of ML applications in various treatment contexts, focusing on treatment outcomes such as patient survival, disease recurrence, and treatment‐induced toxicity. It emphasizes the ascending trajectory of research efforts and the prominence of survival analysis as a clinical priority. We analyze the use of several common medical imaging modalities in conjunction with clinical data, highlighting the advantages and complexities inherent in this approach. The research reflects a commitment to advancing patient‐centered care, advocating for expanded research on abdominal and pancreatic cancers. While data collection, patient privacy, standardization, and interpretability present significant challenges, leveraging ML in radiotherapy holds remarkable promise for elevating precision medicine and improving patient care outcomes.
Determinants of long‐term paramagnetic rim lesion evolution in people with multiple sclerosis
Authors: Reeves Jack A. , Bartnik Alexander , Mohebbi Maryam , Ramanathan Murali , Bergsland Niels , Jakimovski Dejan , Wilding Gregory E. , Salman Fahad , Schweser Ferdinand , Weinstock‐Guttman Bianca , Hojnacki David , Eckert Svetlana , Bagnato Francesca , Dwyer Michael G. , Zivadinov Robert
Published: November 2024

Objective

Baseline paramagnetic rim lesion (PRL) load predicts disease progression in people with multiple sclerosis (pwMS). Understanding how PRLs relate to other known MS‐related factors, and the practical utility of PRLs in clinical trials, is crucial for informing clinical decision‐making and guiding development of novel disease‐modifying treatments (DMTs).

Methods

This study included 152 pwMS enrolled in a larger prospective, longitudinal cohort study who had 3T MRI scans and clinical assessments at baseline and 5‐ or 10‐year follow‐ups. PRLs were identified on baseline 3T quantitative susceptibility maps and classified as persisting, disappearing, or newly appearing at follow‐up. The relationships between PRL evolution and clinical, radiological, environmental, and genetic characteristics were assessed, and clinical trial sample sizes were estimated using PRL appearance or disappearance as outcome measures.

Results

DMT use was associated with lower odds of new PRL appearance (for high‐efficacy DMTs: odds ratio = 0.088, p = 0.024), but not disappearance. Current smoking status was associated with greater baseline PRL number (B = 0.527 additional PRLs, p = 0.013). A 24‐month clinical trial in people with progressive MS for a DMT that doubles the rate of PRL rim disappearance would require an estimated 118 people with progressive MS per group at 80% statistical power.

Interpretation

Early MS diagnosis and subsequent DMT initiation may reduce new chronic active inflammation. However, the utility of PRL disappearance or new PRL appearance as outcome measures in clinical trials is limited by potentially large sample sizes that are needed for moderate efficacy drugs.
Phenotypic and oncological insights in ANNA1 autoimmunity: Age stratification and biomarker analysis
Authors: Paramasivan Naveen Kumar , Masoud Majed , Karsten Carley , Zahid Anza , Kherbek Haidara , Zekeridou Anastasia , Sista Sri Raghav , Dasari Surendra , Knight Andrew M. , Mangioris Georgios , Mills John R. , McKeon Andrew , Pittock Sean J. , Dubey Divyanshu
Published: November 2024

Objective

To describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti‐Hu) autoimmunity.

Methods

A retrospective review of patients with ANNA1‐IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups based on the age of symptom onset. Phage immunoprecipitation sequencing (PhIP‐Seq) and neurofilament light chain (NfL) measurements were done in patient sera/CSF with archived samples.

Results

Of 122 patients, 81 (66%), 20 (16%), and 21 (17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Lung cancer and neuromuscular presentations were more common in older adults (p < 0.001), while limbic encephalitis and neuroblastoma were more common in pediatric patients (p < 0.005). Most young adults (75%) did not have cancer identified. Proportions of patients with a favorable response to immunotherapy were 20%, 30%, and 52% among older adults, young adults, and pediatric groups, respectively. PhIP‐Seq demonstrated significant enrichment for ELAVL4 peptides especially for amino acids 240–289, in the majority of samples evaluated (36/67, 54%). ZIC and SOX2 peptides were significantly enriched in those with central nervous system presentations. Serum NfL levels were elevated in patients with cancer and those with poor long‐term outcomes.

Interpretation

Young adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long‐term outcomes in ANNA1 autoimmunity.
Reliable Automated ECG Arrhythmia Classification Using Reinforced VGG‐27 Neural Network Framework
Authors: Thite Trupti G. , Jagtap Sonal K.
Published: November 2024

Automated categorization of electrocardiogram (ECG) waveforms using deep learning (DL) methods has garnered considerable attention in recent research. However, prevalent DL networks encounter challenges including overfitting, class imbalance, limitations in deeper network training, and high computational demands. To address these issues, this study proposes an Automated ECG Arrhythmia Classification framework employing the Reinforced Visual Geometry Group‐27 (REF‐VGG‐27). Initially, the framework encompasses preprocessing steps such as denoising, R‐peak identification, data balancing, and cross‐validation. For automatic feature extraction and classification, two DL architectures are suggested: a novel hybrid model combining 2D convolutional neural network (2DCNN) with VGG‐16, featuring a deep architecture for extracting morphological characteristics, frequency features related to heart rate variability (HRV), and statistical attributes crucial for identifying atrial fibrillation (AF). Subsequently, to classify arrhythmia patterns, the VGG‐16 Model is employed. Utilizing publicly available ECG image datasets, the proposed model achieved remarkable accuracy benchmarks: 99.61% accuracy, precision of 99.61%, and recall of 99.48%. Comparative analysis with existing approaches substantiates the efficiency and robustness of our model.
Study on Effects of Pulsed Current Treatment on Ultrasonic Welded Joint of Al5052‐H32 Alloy
Authors: Ren Mingming , Li Yongfang , Chen Hao , Xu Sha , Zhang Ruoping , Yang Yali
Published: November 2024

The effect of pulse current on the mechanical properties of ultrasonic welded joints of 5052‐H32 aluminum alloy (Al5052‐H32) plate with a thickness of 2 mm is investigated experimentally. First, ultrasonic lap welding is performed to prepare the welded joint. Then, the pulsed current with different current densities and durations is applied to the welded joint. The impact of pulsed current on the properties of the welded joints is evaluated through tensile lap shear testing, observation using a metallographic microscope, and hardness testing. In the results, it is indicated that the tensile lap shear strength, elongation, and hardness of the welded joints can be improved by applying pulsed current properly. However, excessive input of electrical energy can lead to a decrease in the mechanical properties of the welded joints. Compared to the joint without pulse current treatment, the microstructure shows significant healing of the weld seam under the action of pulsed current. The feasibility of enhancing the mechanical performance of ultrasonically welded joints through the utilization of pulsed current is highlighted by these findings.
Effect of Particle Morphology and Added Gallium on Reactivity of Aluminum Powders
Authors: Gandhi Purvam Mehulkumar , Schoenitz Mirko , Dreizin Edward L.
Published: November 2024

Micron‐sized powders of neat aluminum and aluminum combined with 5 wt% gallium are prepared as flakes and spherical composites by emulsion‐assisted milling. Such powders are of interest as high‐energy‐density fuel additives to solid propellants, explosives, and pyrotechnics. Added gallium does not affect the size or shape of the prepared composites; it also does not change appreciably the oxidation kinetics of the prepared powders. All milled powders ignite readily when coated on an electrically heated filament, unlike the starting aluminum powder. Powders with added gallium ignite at slightly lower temperatures when heated rapidly. The liquid metal embrittlement effect due to added gallium might have caused a smaller microstrain in the refined, milled powders. However, it does not affect the oxidation. Instead, it is proposed that added gallium alters the natural amorphous alumina film, affecting its transition to a crystalline γ‐phase during rapid heating, and thus affecting the powder ignition.
Biodegradable Acid‐Responsive Nanocarrier for Enhanced Antibiotic Therapy Against Drug‐Resistant Helicobacter Pylori via Urease Inhibition
Authors: Fan Huizhen , Wong Ka Ioi , Ma Yingying , Li Ming , Li Hanqing , Wei Li , Wang Shen , Yao Min , Lu Min
Published: November 2024

Metal ion‐based inhibition of urease activity is a promising strategy for treating Helicobacter pylori (H. pylori) infections. However, the challenges of safe delivery and reducing cytotoxicity persist. In this study, an innovative nanocarrier capable of acid‐responsive release of Ag+ and antibiotics is developed, with complete degradation after treatment. Mesoporous organosilica nanoparticle (MON) is encapsulated with hyaluronic acid (HA) to prevent drug leakage and further coated with bacterial outer membrane vesicle (OMV) from Escherichia coli Nissle 1917, creating a nanocarrier with cell‐protective capabilities. Ag+ and antibiotic clarithromycin (CLR) are incorporated into the nanocarrier to form CLR‐Ag+@MON@HA@OMV (CAMO), designed for the targeted treatment of gastric H. pylori infection. The HA encapsulation ensures acid‐responsive release of CLR and Ag+ in the stomach, preventing premature release at non‐inflammatory sites. There is a potential for Ag⁺ in CAMO to replace Ni2⁺ at the active site of urease, enhancing the bactericidal effect of CLR through urease inhibition. Furthermore, the OMV provides additional cytoprotection, mitigating cell damage and inflammation response induced by the H. pylori infection. This study introduces a safe and effective nanocarrier that eradicates H. pylori and alleviates gastric inflammation.
Photothermal/Photodynamic Synergistic Antibacterial Hydrogel Dressing with pH/Glucose Dual Responsive Pirfenidone Release for Diabetic Foot Ulcers
Authors: Pan Guoying , Li Meng , Mu Lei , Huang Ying , Liang Yongping , Guo Baolin
Published: November 2024

Diabetic foot ulcers (DFU) are notoriously challenging to heal due to severe infection, excessive inflammation, and difficulty in angiogenesis. In response to these problems, first, a pH/glucose dual‐responsive hydrogel dressing (HPC) is constructed using dual dynamic crosslinking through Schiff base and phenylboronate ester between m‐aminophenylboronic acid and adipic dihydrazide bifunctionalized hyaluronic acid (AHP) and oxidized chondroitin sulfate (OCS). Then, polydopamine‐reduced graphene oxide compounded glycine‐modified fullerene (GPC) with photothermal/photodynamic synergistic antibacterial properties and the drug pirfenidone (PFD) with pro‐angiogenesis and suppress inflammatory are loaded into the above HPC hydrogel. Based on the response of Schiff base/phenylboronate ester to pH/glucose, the HPC/GPC/PFD (HPCG/PFD) hydrogel can accelerate the release of PFD, thereby improving excessive inflammation and angiogenesis in DFU. In addition, dual dynamic crosslinking provided the hydrogel with good on‐demand removal and self‐healing performance, while GPC brought good tissue adhesion, antioxidation, and electrical conductivity to the hydrogel. The rheology, morphology, mechanical properties, swelling, degradation, and biocompatibility of the hydrogel have been well verified. Finally, in the DFU model of rats, this hydrogel can promote wound repair by reducing infection and inflammation, accelerating wound closure, and enhancing epidermal regeneration, collagen deposition, and angiogenesis, showing promoting effect on diabetic wound healing.
Cordycepin‐Loaded Dental Pulp Stem Cell‐Derived Exosomes Promote Aged Bone Repair by Rejuvenating Senescent Mesenchymal Stem Cells and Endothelial Cells
Authors: Wang Yu , Jin Shanshan , Guo Yaru , Zhu Lisha , Lu Yilong , Li Jing , Heng Boon Chin , Liu Yan , Deng Xuliang
Published: November 2024

Aging impairs bone marrow mesenchymal stem cell (BMSC) functions as well as associated angiogenesis which is critical for bone regeneration and repair. Hence, repairing bone defects in elderly patients poses a formidable challenge in regenerative medicine. Here, the engineered dental pulp stem cell‐derived exosomes loaded with the natural derivative of adenosine Cordycepin (CY@D‐exos) are fabricated by means of the intermittent ultrasonic shock, which dually rejuvenates both senescent BMSCs and endothelial cells and significantly improve bone regeneration and repair in aged animals. CY@D‐exos can efficiently overcome the senescence of aged BMSCs and enhance their osteogenic differentiation by activating NRF2 signaling and maintaining heterochromatin stability. Importantly, CY@D‐exos also potently overcomes the senescence of vascular endothelial cells and promotes angiogenesis. In vivo injectable gelatin methacryloyl (GelMA) hydrogels with sustained release of CY@D‐exos can accelerate bone injury repair and promote new blood vessel formation in aged animals. Taken together, these results thus demonstrate that cordycepin‐loaded dental pulp stem cell‐derived exosomes display considerable potential to be developed as a next‐generation therapeutic agent for promoting aged bone regeneration and repair.
Multifunctional Polysaccharide Self‐Healing Wound Dressing: NIR‐Responsive Carboxymethyl Chitosan / Quercetin Hydrogel
Authors: Xu Qiuting , Su Wei , Huang Cuilan , Zhong Haiyi , Huo Lini , Cai Jinyun , Li Peiyuan
Published: November 2024

As the misuse of antibiotics increases bacterial resistance, the treatment of infected wounds caused by bacteria encounters significant challenges. Conventional antimicrobial dressings often fall short in their ability to inhibit bacterial infections while simultaneously promoting wound healing. To address this issue, a polysaccharide self‐healing hydrogel (CPP@PDA/Que3) wound dressing is successfully developed by incorporating quercetin and polydopamine nanoparticles into a carboxymethyl chitosan matrix. The dressing can be easily injected locally to create a protective barrier over the wound, effectively stopping bleeding and rapidly inhibiting inflammation. Furthermore, the CPP@PDA/Que3 hydrogel exhibits remarkable antioxidant and antibacterial properties, stemming from the combination of quercetin and near‐infrared (NIR) photothermal therapy. It demonstrates the ability to eliminate 99.52% of Staphylococcus aureus and 99.39% of Escherichia coli in in vitro antibacterial experiments. Additionally, the in vivo wound healing experiment shows a healing rate of ≈97%. The experimental results indicate that under NIR laser (808 nm) irradiation, the polysaccharide‐based hydrogel dressing significantly inhibits bacterial growth, reduces oxidative stress, expedites angiogenesis, and thereby accelerates the transition from inflammation to wound healing. In summary, the CPP@PDA/Que3 hydrogel exhibits significant potential as a wound dressing, providing a novel approach for clinically advancing the treatment of bacterial wounds.