bluuebunny/crossref_metadata_2025_split huggingface dataset:
Democratising Food Safety: Why We Need to Look Beyond Government Regulation and Provide a Citizen Right of Action
Authors: Fortin Neal David 
Published: August 2024

AbstractImperfect information on food safety and risk has created a system with less safety than the public wants. Consumers cannot pay for the level of safety they desire. Tort under-compensates for foodborne illness due to difficulty proving causation. When market controls are ineffective at producing the level of safety desired by consumers, the classic approach is government regulation. However, government regulators face challenges that impede the translation of scientific knowledge into regulatory controls. This often results in an equilibrium of private interests and bureaucratic interests rather than the public interest. To restore republican deliberation on food safety we need greater citizen involvement in the decision-making. Access to the courts is an effective means for citizens to participate directly in the decisions affecting food safety; thus, a private cause of action to our national food safety laws is proposed.
Mind the Gap: Assessing Member States’ Implementation of Farm to Farm-to-Fork Targets within the 2023–2027 Common Agricultural Policy
Authors: Mezzacapo Enrico 
Published: August 2024

AbstractThis work has the aim of dissecting the legal and policy dress designed for the new “Green” Common Agricultural Policy (CAP 2023–27) across the proposed CAP Strategic plans (CSPs) of the EU member states. The analysis is carried out through the lens of a special inquiry: the consistency and coherence between the CAP and the perspective of the Green Deal and its satellite strategies, among all the Farm to Fork Strategy (F2F) and Biodiversity Strategy for 2030, for transition to a resilient and Sustainable food system. The F2F proposes a roadmap of interventions and sets specific goals to reach such a transition. Within these interventions, a renewed CAP is the first stage through which the direction undertaken by the EU can be measured. Following the new CAP delivery model, this work will investigate the national CSPs and address the consistency of the CAP financial instruments utilised to fulfill the social, economic and environmental objectives of the CAP according to the ambition of the F2F and other key strategies.
How should we estimate inverse probability weights with possibly misspecified propensity score models?
Authors: Katsumata Hiroto 
Published: August 2024

Abstract
Inverse probability weighting is a common remedy for missing data issues, notably in causal inference. Despite its prevalence, practical application is prone to bias from propensity score model misspecification. Recently proposed methods try to rectify this by balancing some moments of covariates between the target and weighted groups. Yet, bias persists without knowledge of the true outcome model. Drawing inspiration from the quasi maximum likelihood estimation with misspecified statistical models, I propose an estimation method minimizing a distance between true and estimated weights with possibly misspecified models. This novel approach mitigates bias and controls mean squared error by minimizing their upper bounds. As an empirical application, it gives new insights into the study of foreign occupation and insurgency in France.
L-asparaginase induces IP3R-mediated ER Ca2+ release by targeting µ-OR1 and PAR2 and kills acute lymphoblastic leukemia cells
Authors: Lee Jung Kwon , Kamran Hamza , Lee Ki-Young 
Published: August 2024

AbstractL-asparaginase is a standard therapeutic option for acute lymphoblastic leukemia (aLL), a hematologic cancer that claims the most lives of pediatric cancer patients. Previously, we demonstrated that L-asparaginase kills aLL cells via a lethal rise in [Ca2+]i due to IP3R-mediated ER Ca2+ release followed by calpain-1-Bid-caspase-3/12 activation (Blood, 133, 2222-2232). However, upstream targets of L-asparaginase that trigger IP3R-mediated ER Ca2+ release remain elusive. Here, we show that L-asparaginase targets µ-OR1 and PAR2 and induces IP3R-mediated ER Ca2+ release in aLL cells. In doing so, µ-OR1 plays a major role while PAR2 plays a minor role. Utilizing PAR2- and µ-OR1-knockdown cells, we demonstrate that L-asparaginase stimulation of µ-OR1 and PAR2 relays its signal via Gαi and Gαq, respectively. In PAR2-knockdown cells, stimulation of adenylate cyclase with forskolin or treatment with 8-CPT-cAMP reduces L-asparaginase-induced µ-OR1-mediated ER Ca2+ release, suggesting that activation of µ-OR1 negatively regulates AC and cAMP. In addition, the PKA inhibitor 14-22 amide (myr) alone evokes ER Ca2+ release, and subsequent L-asparaginase treatment does not induce further ER Ca2+ release, indicating the involvement of PKA inhibition in L-asparaginase-induced µ-OR1-mediated ER Ca2+ release, which can bypass the L-asparaginase-µ-OR1-AC-cAMP loop. This coincides with (a) the decreases in PKA-dependent inhibitory PLCβ3 Ser1105 phosphorylation, which prompts PLCβ3 activation and ER Ca2+ release, and (b) BAD Ser118 phosphorylation, which leads to caspase activation and apoptosis. Thus, our findings offer new insights into the Ca2+-mediated mechanisms behind L-asparaginase-induced aLL cell apoptosis and suggest that PKA may be targeted for therapeutic intervention for aLL.
Efficacy of an AAV vector encoding a thermostable form of glucocerebrosidase in alleviating symptoms in a Gaucher disease mouse model
Authors: Milenkovic Ivan , Blumenreich Shani , Hochfelder Ariel , Azulay Aviya , Biton Inbal E. , Zerbib Mirie , Oren Roni , Tsoory Michael , Joseph Tammar , Fleishman Sarel J. , Futerman Anthony H. 
Published: August 2024

AbstractAlmost all attempts to date at gene therapy approaches for monogenetic disease have used the amino acid sequences of the natural protein. In the current study, we use a designed, thermostable form of glucocerebrosidase (GCase), the enzyme defective in Gaucher disease (GD), to attempt to alleviate neurological symptoms in a GD mouse that models type 3 disease, i.e. the chronic neuronopathic juvenile subtype. Upon injection of an AAVrh10 (adeno-associated virus, serotype rh10) vector containing the designed GCase (dGCase) into the left lateral ventricle of Gba−/−;Gbatg mice, a significant improvement in body weight and life-span was observed, compared to injection of the same mouse with the wild type enzyme (wtGCase). Moreover, a reduction in levels of glucosylceramide (GlcCer), and an increase in levels of GCase activity were seen in the right hemisphere of Gba−/−;Gbatg mice, concomitantly with a significant improvement in motor function, reduction of neuroinflammation and a reduction in mRNA levels of various genes shown previously to be elevated in the brain of mouse models of neurological forms of GD. Together, these data pave the way for the possible use of modified proteins in gene therapy for lysosomal storage diseases and other monogenetic disorders.
Intermediate phenotype between CMT2Z and DIGFAN associated with a novel MORC2 variant: a case report
Authors: Hanada Kenta , Osaki Yusuke , Miyamoto Ryosuke , Muto Kohei , Haji Shotaro , Nazere Keyoumu , Kuwano Yuki , Morino Hiroyuki , Azuma Yoshiteru , Miyatake Satoko , Matsumoto Naomichi , Izumi Yuishin 
Published: August 2024

Abstract
Charcot-Marie-Tooth disease type 2Z is caused by MORC2 mutations and presents with axonal neuropathy. MORC2 mutations can also manifest as developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN). We report a patient exhibiting an intermediate phenotype between these diseases associated with a novel MORC2 variant. A literature review revealed that the genotype‒phenotype correlation in MORC2-related disorders is complex and that the same mutation can cause a variety of phenotypes.
Risk willingness in multiple system atrophy and Parkinson’s disease understanding patient preferences
Authors: Bernhardt Alexander Maximilian , Oeller Marc , Friedrich Isabel , Kocakavuk Emre , Nachman Eliana , Peikert Kevin , Roderigo Malte , Rossmann Andreas , Schröter Tabea , Wilhelm Lea Olivia , Prell Tino , van Riesen Christoph , Nieweler Johanna , Katzdobler Sabrina , Weiler Markus , Jacobi Heike , Warnecke Tobias , Claus Inga , Palleis Carla , Breimann Stephan , Falkenburger Björn , Brandt Moritz , Hermann Andreas , Rumpf Jost-Julian , Claßen Joseph , Höglinger Günter , Gandor Florin , Levin Johannes , Giese Armin , Janzen Annette , Oertel Wolfgang Hermann 
Published: August 2024

AbstractDisease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson’s Disease (PD) are in early phases of clinical testing. Involving patients’ preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects. Demonstrating a non-gaussian distribution, risk willingness varied markedly within, and between groups. MSA patients accepted a median 1% risk [interquartile range: 0.001–25%] of sudden death for a 99% [interquartile range: 99.999–75%] chance of cure, while PD patients reported a median 0.055% risk [interquartile range: 0.001–5%]. Contrary to our hypothesis, a considerable proportion of MSA patients, despite their substantially impaired quality of life, were not willing to accept increased therapy-associated risks. Satisfaction with life situation, emotional, and nonmotor disease burden were associated with MSA patients’ risk willingness in contrast to PD patients, for whom age, and disease duration were associated factors. An individual approach towards MSA and PD patients is crucial as direct inference from disease (stage) to therapy-associated risk willingness is not feasible. Such studies may be considered by regulatory agencies in their approval processes assisting with the weighting of safety aspects in a patient-centric manner. A systematic quantitative assessment of patients’ risk willingness and associated features may assist physicians in conducting individual consultations with patients who have MSA or PD by facilitating communication of risks and benefits of a treatment option.
Insights gained from computational modeling of YAP/TAZ signaling for cellular mechanotransduction
Authors: Jafarinia Hamidreza , Khalilimeybodi Ali , Barrasa-Fano Jorge , Fraley Stephanie I. , Rangamani Padmini , Carlier Aurélie 
Published: August 2024

AbstractYAP/TAZ signaling pathway is regulated by a multiplicity of feedback loops, crosstalk with other pathways, and both mechanical and biochemical stimuli. Computational modeling serves as a powerful tool to unravel how these different factors can regulate YAP/TAZ, emphasizing biophysical modeling as an indispensable tool for deciphering mechanotransduction and its regulation of cell fate. We provide a critical review of the current state-of-the-art of computational models focused on YAP/TAZ signaling.
Theoretical model of donor–donor and donor–acceptor energy transfer on a nanosphere
Authors: Synak Anna , Kułak Leszek , Bojarski Piotr 
Published: August 2024

AbstractIn this study, we introduce a novel advancement in the field of theoretical exploration. Specifically, we investigate the transfer and trapping of electronic excitations within a two-component disordered system confined to a finite volume. The implications of our research extend to energy transfer phenomena on spherical nanoparticles, characterized by randomly distributed donors and acceptors on their surface. Utilizing the three-body Padé approximant technique, previously employed in single-component systems, we apply it to address the challenge of trapping within our system. To validate the robustness of our model, we conduct Monte Carlo simulations on a donor–acceptor system positioned on a spherical nanoparticle. In particular, very good agreement between the model and Monte Carlo simulations has been found for donor fluorescence intensity decay.
Augmentative and Alternative Communication Interventions in Critical and Acute Care With Mechanically Ventilated and Tracheostomy Patients: A Scoping Review
Authors: LaValley Mimi , Chavers-Edgar Tiffany , Wu Mengxuan , Schlosser Ralf , Koul Rajinder 
Published: August 2024

Purpose:
Communication with nonspeaking patients is a critical challenge of person-centered care. This scoping review aimed to map the literature on augmentative and alternative communication (AAC) interventions for nonspeaking mechanically ventilated and tracheostomy patients in critical and acute care settings.

Method:
Electronic database, ancestry, and forward citation searches were conducted using eligibility criteria established a priori. Data were extracted, synthesized, and summarized according to scoping review methodology. Studies were categorized by type of intervention and summarized in terms of purpose, participants, design, quality appraisal (including validity and reliability of selected efficacy measures), and efficacy.

Results:
Small-to-large treatment effect sizes indicated demonstrable impact on patient health and communication efficacy with high-tech and no-tech visual interface–based interventions and systematic nurse training interventions. Treatment effects primarily pertained to dependent variables of patient anxiety, communication satisfaction, comfort, symptom self-reporting, and nursing practice changes.

Conclusions:
There is a paucity of high-quality AAC intervention research for mechanically ventilated and tracheostomy patients in critical and acute care settings. Emergent evidence suggests that select visual interface and nurse training interventions can impact efficacy of patient–provider communication and patients' overall health.

Supplemental Material:

https://doi.org/10.23641/asha.26506102
Targeting Phonology or Semantics to Improve Reading Aloud Response Times and Accuracy: A Case Series Investigation of Stroke Survivors With Aphasia
Authors: Boukrina Olga , Madden Elizabeth B. , Giordano Nicole , Karim Dima , Staples Ryan , Graves William W. 
Published: August 2024

Purpose:
Acquired reading deficits, or alexia, affect a significant proportion of individuals with aphasia. We sought to improve treatment for alexia by targeting specific cognitive information-processing components critical to reading (i.e., phonology or semantics).

Method:

To target either phonological or semantic processing, we administered two anomia treatments, phonomotor treatment (PMT) and semantic feature analysis, modified to include a focus on reading throughout the therapy. Chronic left-hemisphere stroke survivors (
N
= 5) completed one or two 60-hr treatment rounds. Based on predictions from a computational reading model, three participants received the treatment recommended for their specific reading challenges (e.g., PMT for phonological deficits), while two participants had the nonrecommended treatment first, followed by the recommended model-matched treatment. Changes in reading aloud accuracy and response times (RTs) from before to after treatment were examined as a function of matching treatment to the deficit profile, type of treatment, therapy round, and word characteristics.

Results:
Participants' reading aloud accuracy improved after treatment relative to baseline with higher accuracy for high-frequency words and shorter words. After the first treatment round, participants' accuracy and RT improved, irrespective of whether treatment was matched to the deficit profile. Furthermore, participants who completed the second treatment round continued achieving accuracy gains. Following treatment, participants demonstrated enhanced reading efficiency and generalized improvements on the selected sections of the Woodcock Reading Mastery Test.

Conclusions:
While larger studies are needed to test for the effects of matching treatment type to the deficit profile, we conclude that treatments targeting specific information-processing components can effectively improve reading. Doubling the treatment dose offers small but significant gains.

Supplemental Material:

https://doi.org/10.23641/asha.26517319
Articulation Assessment for Tongue Cancer Patients: Using Consonant Production Performance to Capture Speech Deficits
Authors: Xie Tongtong , Li Yi , Xiao Yudong , Zheng Huayong , Liao Guiqing , Lu Shuo 
Published: August 2024

Purpose:
The purpose of this study was to thoroughly analyze postoperative consonant errors by tongue cancer (TC) patients with speech disorders and also to investigate the correlation between the pathological factors and the speech performance using our Consonant-based Articulation Assessment Battery (CAAB).

Method:
The participants were 57 monolingual Mandarin TC patients (26 women, 31 men) after surgery (aged 20–80 years). All participants were literate and had normal vision and hearing, enabling them to comprehend and comply with our instructions. In order to quickly evaluate their articulation performance based on the place and manner of articulation, they were instructed to pronounce the characters in CAAB. The analysis removed speech samples impacted by speakers' dialects, while recording and documenting all other responses.

Results:
The study uncovered a significant correlation between pathological factors (e.g., size of tongue resection, specific resection site, and tumor size) and the accuracy of consonant articulation. Furthermore, tongue damage predominantly impacts the place of articulation (63.85%) than the manner of articulation (20.78%). The damage in the anterior part of the tongue has the most prominent influence on consonant production.

Conclusions:
CAAB can fast capture the idiosyncratic characteristics of speech production by TC patients, and the articulation deficits are quite different from other types of organic or nonorganic speech disorders, for example, cleft lip and cleft palate. Hence, CAAB can be designated as an assessment tool for articulation disorders caused by stomatognathic damages. Our findings also shed light on the possible oral cancer surgery plan and the postoperative speech rehabilitation training.
Impfen bei pneumologischen Erkrankungen – was, wann und wie?
Authors: Kodde Cathrin , Sander Leif Erik 
Published: August 2024

Was ist neu?
SARS-CoV-2 Im Zuge der COVID-19-Pandemie wurden erstmalig Impfstoffe zugelassen, die auf der mRNA-Technologie beruhen. Dabei kodiert die mRNA für das virale Spike-Protein und es kommt nach der Impfung zur Ausbildung von spezifischen Antikörpern und T-Zellen, welche einen sehr wirksamen Schutz gegen eine schwere Erkrankung und Tod infolge von COVID-19 bewirken. Aufgrund von genetischer Variabilität und rascher Evolution des SARS-CoV-2-Virus entstehen regelmäßig neue Virusvarianten. Die verfügbaren Impfstoffe können vergleichsweise schnell an die saisonal dominierenden Virusvarianten angepasst werden. Für die kommende Wintersaison werden mRNA-Impfstoffe gegen die SARS-CoV-2-Omicron-Sublinie JN.1 empfohlen.
Saisonale Influenza Saisonale Influenzaviren verändern sich saisonal erheblich in ihren antigenen Eigenschaften, sodass jährlich veränderte Impfstoffe zur Auffrischung gegeben werden. Die WHO trifft jeweils im Frühjahr eine Vorhersage und spricht eine Empfehlung für die Hersteller aus, welche genetischen Hämagglutinin- und Neuraminidase-Varianten für den saisonalen Influenzaimpfstoff berücksichtigt werden sollen. Bislang wurden quadrivalente Impfstoffe empfohlen. Für die Saison 2024/2025 auf der Nordhalbkugel wurden trivalente Impfstoffe empfohlen, da seit 2020 die Influenza-B-/Yamagata-Linie nicht mehr zirkuliert. Für die Altersgruppe >60 Jahre ist ein Hochdosis-Impfstoff mit der 4-fachen Antigenmenge empfohlen, der in dieser Altersgruppe eine leichtgradig verbesserte Wirksamkeit zeigt.
Frailty in der Onkologie: Neue Handlungsempfehlungen für die klinische Praxis
Authors: Goede Valentin , Wedding Ulrich 
Published: August 2024

Was ist neu?
Definition von Frailty Als Frailty wird allgemein eine Altersfaktoren geschuldete, gesteigerte Anfälligkeit für Morbidität und Mortalität bezeichnet. Im Kontext onkologischer Behandlungen älterer Menschen erhöht Frailty aber nicht nur die Wahrscheinlichkeit für unerwünschte geriatrietypische Gesundheitsereignisse (z.B. pflegerische Institutionalisierung, Stürze), sondern auch das Risiko für Therapiekomplikationen wie Toxizität und Unterbrechung oder Abbruch der Tumortherapie.
Identifikation von Patienten mit Frailty In der Onkologie sind Assessment und Management von Frailty jetzt unverzichtbare Bestandteile klinischen Handelns. Mehrere prospektive, randomisiert-kontrollierte Studien (RCT) an älteren Patienten mit onkologischer Systemtherapie haben jüngst gezeigt, dass die strukturierte Erfassung von Frailty im Rahmen eines multidimensionalen geriatrischen Assessments, mit anschließender Anpassung von Therapiedosis oder -regime, sowie der Behandlung individueller Frailty-Faktoren dabei hilft, Häufigkeit und Schwere ungünstiger Endpunkte einer onkologischen Therapie zu reduzieren.
Assessment und Management von Frailty im onkologischen Behandlungskontext In neuen Leitlinien der American Society of Clinical Oncology (ASCO) bzw. der Arbeitsgemeinschaft der Medizinischen Fachgesellschaften (AWMF) wurden die Studienergebnisse unlängst aufgenommen und entsprechende Handlungsempfehlungen mit hohem Evidenz- und Empfehlungsgrad ausgesprochen. Um die Implementierung eines gezielten Frailty-Assessments und -Managements in onkologischen Kliniken und Praxen zu erleichtern, wurde von der ASCO ein neues, anwendbares „Praktisches Geriatrisches Assessment“ (PGA) vorgeschlagen.
Lagerungstherapie bei Intensivpatienten
Authors: Hermes Carsten , Nydahl Peter , Grunow Julius J. , Schaller Stefan J. 
Published: August 2024

Was ist neu?
(Früh-)Mobilisation Besonders hervorzuheben ist die differenziertere Betrachtung der Frühmobilisation, die innerhalb der ersten 72 Stunden nach der Aufnahme auf die Intensivstation beginnen soll. Ein Stufenkonzept und das scorebasierte Mobilisationsschema ermöglichen eine verbesserte Rehabilitation der behandelten Personen. Mobilisation soll den Standard darstellen, d.h. eine medizinisch notwendige Immobilisation muss ärztlich angeordnet werden. Die neue Leitlinie gibt Vorschläge für die Therapiedauer und zusätzliche Mobilisationsmaßnahmen, um sicherzustellen, dass die zu behandelnden Personen so oft wie möglich stehen, aktiv vom Bett zum Stuhl transferiert werden oder gehen können. Diese Empfehlungen gelten auch während einer ECMO-Therapie, was die Bedeutung einer frühzeitigen Aktivierung und Rehabilitation betont.
Oberkörper-Hochlagerung Zu den weiteren Neuerungen gehört die Oberkörper-Hochlagerung (OKH) von mind. 40 Grad bei intubierten kritisch Kranken, wobei potenzielle Nebenwirkungen und Risiken sorgfältig abgewogen werden müssen.
Kontinuierliche laterale Rotationstherapie Die Anwendung der kontinuierlichen lateralen Rotationstherapie (KLRT) weist im Vergleich zu anderen Therapien keine bedeutsamen Vorteile auf, führt aber durch die Notwendigkeit einer tiefen Sedierung während der KLRT zu mehr Nachteilen und wird deswegen nicht mehr empfohlen.
Bauchlagerung Die Bauchlagerung ist die empfohlene Therapieoption für invasiv beatmete Personen mit ARDS und eingeschränkter arterieller Oxygenierung (PaO2/FiO2 <150mmHg) für eine Mindestdauer von 12 Stunden, idealerweise 16 Stunden. Besondere Empfehlungen gelten bspw. für COVID-19-Erkrankte mit akutem hypoxischem Lungenversagen, bei denen Bauchlagerungen im Wachzustand („awake proning“) durchgeführt werden sollten.
Hilfsmittel Die Leitlinie befasst sich neu mit Hilfsmitteln und neuromuskulärer Elektrostimulation, die im Rahmen der Lagerungstherapie und vor allem zur (Früh)Mobilisation von intensivpflichtigen Personen eingesetzt werden.