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Trees with weeping shoot architectures are valued for their beauty and serve as tremendous resources for understanding how plants regulate posture control. ThePrunus persica(peach) weeping phenotype, which has elliptical downward arching branches, is caused by a homozygous mutation in theWEEPgene. Until now, little was known about the function of WEEP protein despite its high conservation throughout Plantae. Here, we present the results of anatomical, biochemical, biomechanical, physiological, and molecular experiments that provide insight into WEEP function. Our data suggest that weeping peach does not have defects in branch structure. Rather, transcriptomes from the adaxial (upper) and abaxial (lower) sides of standard and weeping branch shoot tips revealed flipped expression patterns for genes associated with early auxin response, tissue patterning, cell elongation, and tension wood development.This suggests that WEEP promotes polar auxin transport toward the lower side during shoot gravitropic response, leading to cell elongation and tension wood development. In addition, weeping peach trees exhibited steeper root systems and faster root gravitropic response, just as barley and wheat with mutations in theirWEEPhomologEGT2. This suggests that the role of WEEP in regulating lateral organ angles and orientations during gravitropism may be conserved. Additionally, size-exclusion chromatography indicated that WEEP proteins self-oligomerize, like other SAM-domain proteins. This oligomerization may be required for WEEP to function in formation of protein complexes during auxin transport. Collectively, our results from weeping peach provide new insight into polar auxin transport mechanisms associated with gravitropism and lateral shoot and root orientation.

Supplemental Table 3. Primer sequences.

Supplemental Table 2: List of SNPs analyzed.

Supplemental Table 1: Specimen Characteristics.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated peripheral nerve disorder with variable prognosis and long-term dependence on immunotherapy. Frequent assessment of grip strength can be a useful tool to identify intravenous immunoglobulin (IVIG) treatment-related fluctuations (TRFs) and optimize IVIG treatment in real-time, but the long-term implications of TRFs are unknown. We aimed to explore the impact that real-time TRFs had on long-term CIDP prognosis, strength impairment, and disability.This retrospective observational cohort study analyzed standard of care clinical and treatment outcomes in patients who participated in a published prospective study of intra-IVIG-cycle grip strength quantification. Patients were analyzed based upon the presence or absence of TRFs, as determined in the initial prospective study.Data were available for 23 CIDP patients with a mean follow-up period of 44.7 mo. There were no differences in baseline or follow-up strength, disability, or IVIG usage in patients with a low number of fluctuations compared to those with a high number of fluctuations. In both groups, drug-free remission was achieved in about one-third of patients.TRFs are important to identify in order to optimize treatment in real time, but poorly predict long-term disease activity status. The presence of minor TRFs are unlikely to result in substantial accumulation of disability over time. Periodic IVIG optimization trials using objective outcomes are encouraged in all CIDP patients receiving chronic IVIG treatment as a means to identify the lowest effective IVIG dose and frequency.

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated syndrome characterized clinically by weakness and/or numbness that evolves over 2 months or more. The heterogeneity of clinical features necessitates an individualized approach to disease monitoring that takes lessons learned from clinical trials and applies them to clinical practice. Areas covered: This review discusses the importance of clinimetrics and biomarkers in CIDP diagnosis and disease monitoring. Highlighted are the challenges of defining responses to immunotherapy, the usefulness, and limitations of utilizing evidence-based clinical outcome measures during routine clinical care, and the evolving understanding of how diagnostic and disease activity biomarkers may reshape our treatment and disease monitoring paradigms. Expert opinion: Although disability and impairment outcome measures are commonly used in CIDP to indicate disease status, the nonspecific nature of these metrics limits the ability to attribute a change in any given metric to a change in CIDP. This interpretive challenge may be magnified by inconsistencies in the direction of change as well as a strong placebo effect. There is a need to improve our understanding of minimally important changes in existing outcome measures as a means to personalize treatment and to better assess disease activity status with biomarker discovery.

PurposeIn this work, with a goal to ultimately forward the advancement of additive manufacturing research, the author applies the Wheeler-Boettinger-McFadden model through a progressive series of increasingly complex solidification problems illustrating the evolution of both dendritic as well as columnar growth morphologies. For purposes of convenience, the author assumes idyllic solutions (i.e. the excess energies associated with mixing solid and liquid phases can be neglected).Design/methodology/approachIn this work, the author applied the phase-field model through a progressive series of increasingly complex solidification problems, illustrating the evolution of both dendritic as well as columnar growth morphologies. Beginning with a non-isothermal treatment of pure Ni, the author further examined the isothermal and directional solidification of Cu–Ni binary alloys.Findings(1) Consistent with previous simulation results, solidification simulations from each of the three cases revealed the presence of parabolic, dendrite tips evolving along directions of maximum interface energy. (2) For pure Ni simulations, changes in the anisotropy and noise magnitudes resulted in an increase of secondary dendritic branches and changes in the direction of propagation. The overall shape of the primary structure tended also to elongate with increased anisotropy. (3) For simulations of isothermal solidification of Ni–Cu binary alloys, the development of primary and secondary dendrite arm formation followed similar patterns associated with a pure substance. Calculations of dendrite tip velocity tended to increase monotonically with increasing anisotropy in accordance with previous research. (4) Simulations of directional solidification of Ni–Cu binary alloys with a linear temperature profile demonstrated the presence of cellular dendrites with relatively weak side-branching. The occurrence of solute trapping was also apparent between the primary dendrite columns. Dendrite tip velocities increased with increasing cooling rate.Originality/valueThis research, particularly the section devoted to directional solidification of binary alloys, describes a novel numerical framework and platform for the parametric analysis of various microstructural related quantities, including the effects due to changes in temperature gradient and cooling rate. Both the evolution of the phase and concentration are resolved.

Diffuse spinal cord gliomas (SCGs) are rare tumors associated with a high morbidity and mortality that affect both pediatric and adult populations. In this retrospective study, we sought to characterize the clinical, pathological, and molecular features of diffuse SCG in 22 patients with histological and molecular analyses. The median age of our cohort was 23.64 years (range 1-82) and the overall median survival was 397 days. K27M mutation was significantly more prevalent in males compared to females. Gross total resection and chemotherapy were associated with improved survival, compared to biopsy and no chemotherapy. While there was no association between tumor grade, K27M status (p = 0.366) or radiation (p = 0.772), and survival, males showed a trend toward shorter survival. K27M mutant tumors showed increased chromosomal instability and a distinct DNA methylation signature.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic immune-mediated peripheral form of polyneuropathy. No reliable diagnostic biomarkers are available by which to make the diagnosis of CIDP. As a result, diagnosis of the condition can be challenging. Many patients are not recognized early in the disease course, and on the other end of the spectrum both establishing early and accurate diagnosis as well as avoiding misdiagnosis and overtreatment. Identification of the hallmark clinical, electrophysiological, and laboratory features of the disease are critical to facilitate rapid diagnosis, while an understanding of diagnostic pitfalls can help prevent misdiagnosis. Since the original description of CIDP in the 1970s, over 15 sets of diagnostic criteria have been proposed. The criteria published in 2021 by the European Academy of Neurology / Peripheral Nerve Society (EAN/PNS) were developed for use during routine clinical care and are available in the public domain. These criteria provide clinicians with an invaluable resource by which the data collected during the evaluation of the patient with possible CIDP can be interpreted. One point of importance that bridges diagnosis to treatment is objectification of the treatment response. Interpretation of how patients respond to treatment drives both long-term treatment paradigms and the diagnosis at which these treatments are aimed. Although no approach is perfect, utilization of strength impairment and disability outcomes in clinical practice can help unravel the difficulties in interpreting response to treatment. Just as improvement in these outcomes is considered diagnostically supportive, the absence of objective benefit argues against it and should prompt reconsideration of a CIDP diagnosis.

On 5 April 2010, the largest mining disaster in the US since 1970 occurred at the Upper Big Branch Mine in West Virginia. Twenty-five miners were known to have died in the explosion, with the fates of four miners unknown. Families of the twenty-nine miners gathered together at the mine site as they awaited word as to which of the miners died and who had survived. On 6 April, the Red Cross invited representatives from the West Virginia Council of Churches to the mine site to help organize pastoral support for the families. On the evening of 10 April, five days after the explosion, word came that all of the 29 miners had died in the initial explosion. Governor Joe Manchin declared, on 25 April, for a public memorial service for the miners—an event attended by several thousand worshipers and led by clergy, denominational leaders, and public officials, including President Barack Obama, Vice President Joe Biden, Senator Robert C. Byrd, and Governor Manchin. This collaborative essay traces how the pastoral, political, and relational response to trauma shaped this liturgical form. Given the oral traditions of the region, narrative will be one of the primary structures for analysis, and testimony is central to this public worship. A public secular ritual with its goals of unity and inter-riting of distinct religious voices and identities will provide a grammar for reading the service.

Background For many chronic immune system disorders, the available treatments provide several options for route of administration. The objective of this systematic literature review is to inform discussions about therapy choices for individual patients by summarizing the available evidence regarding the preferences of patients with chronic immune system disorders for intravenous (IV) or subcutaneous (SC) administration. Methods Searches of the MEDLINE, Embase and Cochrane Library databases were conducted using terms designed to capture studies reporting patient preferences between IV and SC therapy published in English. Relevant studies were limited to those in which mode of administration, including treatment frequency and setting, was the main difference between comparators. Results In total, 49 studies were included in the review. Among 18 studies that compared IV and SC immunoglobulin therapy, 16 found patients to prefer the SC administration route. The results of the 31 studies comparing IV infusion and SC injection of non-immunoglobulin therapies were mixed, with patients favoring SC administration in 20, IV infusion in seven, and having no overall preference in four. Patient experience had a strong effect on preferences, with treatment-experienced patients preferring their current administration route in most studies. Patients preferring SC administration tended also to prefer treatment at home, mainly due to the convenience and comfort of home treatment and the avoidance of having to attend hospital. By contrast, patients preferring IV infusion tended to cite the lower treatment frequency and a dislike of self-injecting, and preferred hospital treatment, mainly due to the presence of healthcare professionals and resulting feelings of safety. Conclusion In general patients with chronic immune system disorders tend to be more likely to choose SC administration than IV infusion, but preferences may vary according among individuals. These findings may assist discussions around appropriate treatment choices for each patient.

This article asks how costly targeted trade sanctions imposed by the US government are for domestic firms. I argue that, as a result of sanctions, the firm value of US companies that have supply relationships with sanctioned entities is likely to suffer from lost revenue, reputational damage, and business model uncertainty. I test this expectation by applying an event study to the important case of targeted trade sanctions against Chinese technology companies. I find that sanctions against these companies reduced their US suppliers’ risk-adjusted stock returns by 220 basis points. Firm-level cross-sectional analysis shows that businesses with stronger ties to the sanctioned entities are more negatively affected, which supports the direct connection between sanctions and relevant suppliers. Measuring the domestic economic ramifications of sanctions for the sender country has been elusive. These findings, which are statistically and economically significant, indicate that US companies face notable costs from sanctions against internationally active firms.

Introduction The extent to which work productivity, emotional well-being, social interactions, and family life are impacted in patients who self-identify as having chronic inflammatory demyelinating polyneuropathy (CIDP) is not well characterized. Methods Data from an online survey of 595 individuals with self-reported CIDP, recruited by the Guillain–Barré syndrome (GBS)/CIDP Foundation, were used to assess disease and treatment burden. A total of 37% of patients were classified as “likely”, 34% as “somewhat likely”, and 28% as “unlikely” CIDP. Results Of ten symptoms that patients with CIDP may experience, each symptom was experienced by 77–94% of “likely”, 79–96% of “somewhat likely”, and 66–91% of “unlikely” patients. In “likely” CIDP patients 44% stopped working because of their symptoms and 24% moved to a new home. The most common treatments were intravenous immunoglobulin (IVIg) infusion and corticosteroids. IVIg was associated with venous access issues and work/school absenteeism. Conclusions CIDP diagnostic confirmation was not performed in any of the survey respondents. Our results do not add any knowledge on the diagnosis or treatment of CIDP. Our findings do provide insight into the symptoms that patients that think they have CIDP or have been told they have CIDP experience, explores how patients that are labeled as having CIDP view treatment expectations, and highlights how these symptoms affect home and work life. We hope that the findings are constructively used to get patients the services they need to improve quality of life, maintain employment, and ensure a safe home environment regardless of diagnostic accuracy.

This narrative review provides an overview of specific outcomes that are appropriate for chronic inflammatory demyelinating polyneuropathy monitoring during routine clinical care and highlights the minimum clinically important difference, if known. Importance Identifying clinical change in many neurologic diseases, including chronic inflammatory demyelinating polyneuropathy (CIDP), can be challenging. At the same time, how change is defined heavily influences a patient's diagnostic and treatment pathway. It can be especially problematic when equivocal subjective observations are interpreted as clinically meaningful and then used to make diagnostic and treatment decisions. Change in clinical trials is strictly defined by a preselected metric, but there is a perception that formal outcomes collection during routine clinical care is neither feasible nor necessary. Given the importance placed on how change is interpreted, there is a need to select assessments that can be applied to routine care that are representative of the neurologic disease state. Observations For an outcome measure to be useful during clinical trials, it must have good reliability, validity, be responsive to change, and have clinical meaning. To be useful during routine clinical care, the assessment must additionally be easy to collect without the need for extensive training or equipment and should provide an immediately available result that can be rapidly quantified and interpreted. Chronic inflammatory demyelinating polyneuropathy is clinically heterogeneous and so is best evaluated with a diverse group of assessment tools. Assessing strength impairment, disability, and quality of life is ideally suited for everyday practice when caring for patients with CIDP. While electrophysiologic studies, imaging, cerebrospinal fluid, and nodal/paranodal antibodies can provide diagnostic data, they are less practical and helpful longitudinal assessment tools. Conclusions and Relevance Sound clinimetric outcome measures in CIDP are widely available and have the potential to help clinicians objectify treatment response and disease progression. Such data are critically important when justifying the need for ongoing or periodic immunotherapy, documenting relapse or deterioration, or providing reassurance of disease improvement, stability, or remission.

Background Activation of the mammalian target of rapamycin (mTOR) pathway is observed in neurofibromatosis type 1 (NF1) associated low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied in this population. We evaluate the efficacy of the orally administered mTOR inhibitor everolimus for radiographically progressive NF1-associated pediatric LGGs. Methods Children with radiologic-progressive, NF1-associated LGG and prior treatment with a carboplatin-containing chemotherapy were prospectively enrolled on this phase II clinical trial to receive daily everolimus. Whole blood was analyzed for everolimus and markers of phosphatidylinositol-3 kinase (PI3K)/mTOR pathway inhibition. Serial MRIs were obtained during treatment. The primary endpoint was progression-free survival at 48 weeks. Results Twenty-three participants (median age, 9.4 y; range, 3.2–21.6 y) were enrolled. All participants were initially evaluable for response; 1 patient was removed from study after development of a malignant peripheral nerve sheath tumor. Fifteen of 22 participants (68%) demonstrated a response, defined as either shrinkage (1 complete response, 2 partial response) or arrest of tumor growth (12 stable disease). Of these, 10/15 remained free of progression (median follow-up, 33 mo). All remaining 22 participants were alive at completion of therapy. Treatment was well tolerated; no patient discontinued therapy due to toxicity. Pharmacokinetic parameters and pre-dose concentrations showed substantial between-subject variability. PI3K/mTOR pathway inhibition markers demonstrating blood mononuclear cell mTOR pathway inactivation was achieved in most participants. Conclusion Individuals with recurrent/progressive NF1-associated LGG demonstrate significant disease stability/shrinkage during treatment with oral everolimus with a well-tolerated toxicity profile. Everolimus is well suited for future consideration as upfront or combination therapy in this patient population.

The cost of delivered H2 using the liquid-distribution pathway will approach $4.3–8.0/kg in the USA and 26–52 RMB/kg in China by around 2030, assuming large-scale adoption. Historically, hydrogen as an industrial gas and a chemical feedstock has enjoyed a long and successful history. However, it has been slow to take off as an energy carrier for transportation, despite its benefits in energy diversity, security and environmental stewardship. A key reason for this lack of progress is that the cost is currently too high to displace petroleum-based fuels. This paper reviews the prospects for hydrogen as an energy carrier for transportation, clarifies the current drivers for cost in the USA and China, and shows the potential for a liquid-hydrogen supply chain to reduce the costs of delivered H2. Technical and economic trade-offs between individual steps in the supply chain (viz. production, transportation, refuelling) are examined and used to show that liquid-H2 (LH2) distribution approaches offer a path to reducing the delivery cost of H2 to the point at which it could be competitive with gasoline and diesel fuel.

The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than in Asian population. However, E&NA cooperative groups have simultaneously developed with success treatment strategies with specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis with an endoscopic biopsy and/or cerebrospinal fluid (CSF) and/or serum analysis, deferring the need to perform a radical surgery. Depending on markers and/or histological characteristics, patients are treated as either germinoma or non-germinomatous germ cell tumors (NGGCT). Metastatic disease is defined by a positive CSF cytology and/or distant drops in craniospinal MRI. The combination of surgery and/or chemotherapy and radiation therapy is tailored according to grouping and staging. With more than 90% 5-year event-free survival (EFS), localized germinomas can be managed without aggressive surgery, and benefit from chemotherapy followed by whole ventricular irradiation with local boost. Bifocal germinomas are treated as non-metastatic entities. Metastatic germinomas may be cured with craniospinal irradiation. With a 5-year EFS over 70%, NGGCT benefit from chemotherapy followed by delayed surgery in case of residual disease, and some form of radiotherapy. Future strategies will aim at decreasing long-term side effects while preserving high cure rates.

BACKGROUND: Central nervous system (CNS) germinomas are treatment-sensitive tumors with excellent survival outcomes. Current treatment strategies combine chemotherapy with radiotherapy (RT) in order to reduce the field and dose of RT. Germinomas originating in the basal ganglia/thalamus (BGTGs) have proven challenging to treat given their rarity and poorly defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have all been utilized; however, the best treatment strategy remains unclear. METHODS: Retrospective multi-institutional analysis has been conducted across 18 institutions in four countries. RESULTS: For 43 cases of non-metastatic BGTGs, the 5- and 10-year event-free survival (EFS) were 85.8% and 81.0%, respectively, while the 5- and 10-year overall survival (OS) were 100%, and 95.5%, respectively (one patient fatality from unrelated cause). Median RT doses were as follows: CSI: 2250 cGy/cGy(RBE) (1980 to 2400 cGy/cGy[RBE]), WBI: 2340 (1800 to 3000 cGy/cGy[RBE]), WVI: 2340 cGy/cGy(RBE) (1800 to 2550 cGy/cGy[RBE]), focal: 3600 cGy (3060 to 5400 cGy). Thirty-eight patients (90.5%) received chemotherapy. There was no statistically significant difference in the EFS based on initial field extent (p=0.84). Nevertheless, no relapses were reported in patients who received CSI or WBI. Chemotherapy alone had significantly inferior EFS compared to combined therapy (p=0.0092), but patients were salvageable with RT. CONCLUSION: Patients with BGTGs have excellent outcomes and RT proved to be an integral component of the treatment plan. This group of patients should be included in future prospective clinical trials and the best RT field should be investigated further.

Background and purpose The aim of this study was to determine the frequency of over‐ and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to identify related diagnostic pitfalls. Methods We conducted a retrospective study in Dutch patients referred to the Erasmus University Medical Centre Rotterdam between 2011 and 2017 with either a diagnosis of CIDP or another diagnosis that was revised to CIDP. We used the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 diagnostic criteria for CIDP to classify patients into three groups: overdiagnosis, underdiagnosis, or confirmed diagnosis of CIDP. Clinical and laboratory features and treatment history were compared between groups. Results A referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). In the overdiagnosed patients, 20% of muscle weakness was asymmetric, 48% lacked proximal muscle weakness, 29% only had distal muscle weakness, 65% did not fulfil the electrodiagnostic criteria for CIDP, 74% had an elevated cerebrospinal fluid (CSF) protein level, and 97% had another type of neuropathy. In the underdiagnosed patients, all had proximal muscle weakness, 50% had a clinically atypical CIDP, all fulfilled the electrodiagnostic criteria for CIDP, and 25% had an increased CSF protein level. Conclusion Over‐ and underdiagnosis of CIDP is common. Diagnostic pitfalls include lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on CSF protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy., Over‐ and underdiagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is common. A referral diagnosis of CIDP was revised in 32% of patients (31/96; overdiagnosis). Of 81 patients diagnosed with CIDP, 16 (20%) were referred with another diagnosis (underdiagnosis). Almost all overdiagnosed patients had other forms of neuropathy, while underdiagnosed patients were referred with various neurological disorders. Diagnostic pitfalls included lack of attention to proximal muscle weakness as a diagnostic hallmark of CIDP, insufficient recognition of clinical atypical phenotypes, overreliance on cerebrospinal fluid protein levels, misinterpretation of nerve conduction studies and poor adherence to electrodiagnostic criteria, and failure to exclude other causes of polyneuropathy.

The convective structure and heat transfer characteristics of evaporating films under conditions of cyclical superheating were examined experimentally. An isolated closed test cell allowed the film...

Proper water management in Polymer Exchange Membrane (PEM) fuel cell is important to achieve high performance. Understanding the percolation of the produced water at the cathode catalyst layer (CL), is critical for any robust water management technique. The CL consists of a complex structure to allow reactants to pass through and reach the reaction catalyst site. The complex structure is made by a support structure (mostly carbon) that allows the transport of electrons, an ionomer that conducts protons, and voids that have the double role of oxygen breathing and exit paths for the generated water. In this work, a pseudo-Hele–Shaw experimental setup is used to investigate immiscible fluid displacement inside the CL under controlled conditions. Since water can be retained by ionomer, making it swell and caused a shift in the pore size distribution, fluor-inert is used as a working fluid. The evolution of percolation pressure and the projected area of the injected fluid are recorded simultaneously. Preliminary results show a high consistency in the measured data at high flow rate percolation. However, at low flow rate there is some variation in the data due to relative humidity effect. The experimental data is considered as an input to the (Ce-t^*) scale. This scaling has been previously developed (Medici & Allen, 2011) to study two phase flow in thin porous layers. The dimensionless energy scale (Ce) based on the ratio between the injected and dissipated energies. The other dimensionless time scale (t^*) is arises from the important of the time of percolation, where in capillary regime is in order of hours while in stable displacement is in order of minutes, so it characterizes the relative effects of viscous and capillary effect. This scaling collapses transient pressure and saturation to a linear, non-dimensional and unique correlation for each material.

Perfluorinated sulfonic-acid (PFSA) ionomers are members of a class of ion-conductive polymers that are commonly used as a proton-exchange membrane or catalyst layers in polymer-electrolyte fuel cells. Numerous studies have been undertaken to understand how the structure of PFSA ionomers with thickness of 1 to 200 µm and their water uptake affect the material properties and the performance of fuel cells. Thin film confinement affects the hydration behavior of thin film ionomers; the deviation from transport properties are still unclear. Advanced tools have been used to study water uptake of sub-micron PSFA ionomers at different humidity levels; however, their temporal resolution are of the order of 1 minute. Label free, high-speed Surface Plasmon Resonance imaging (SPRi) is proposed to provide a 3D map of a thin film (